Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
A single-chain polypeptide growth factor that plays a significant role in the process of WOUND HEALING and is a potent inducer of PHYSIOLOGIC ANGIOGENESIS. Several different forms of the human protein exist ranging from 18-24 kDa in size due to the use of alternative start sites within the fgf-2 gene. It has a 55 percent amino acid residue identity to FIBROBLAST GROWTH FACTOR 1 and has potent heparin-binding activity. The growth factor is an extremely potent inducer of DNA synthesis in a variety of cell types from mesoderm and neuroectoderm lineages. It was originally named basic fibroblast growth factor based upon its chemical properties and to distinguish it from acidic fibroblast growth factor (FIBROBLAST GROWTH FACTOR 1).
A family of small polypeptide growth factors that share several common features including a strong affinity for HEPARIN, and a central barrel-shaped core region of 140 amino acids that is highly homologous between family members. Although originally studied as proteins that stimulate the growth of fibroblasts this distinction is no longer a requirement for membership in the fibroblast growth factor family.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Specific molecular sites or structures on cell membranes that react with FIBROBLAST GROWTH FACTORS (both the basic and acidic forms), their analogs, or their antagonists to elicit or to inhibit the specific response of the cell to these factors. These receptors frequently possess tyrosine kinase activity.
A 17-kDa single-chain polypeptide growth factor that plays a significant role in the process of WOUND HEALING and is a potent inducer of PHYSIOLOGIC ANGIOGENESIS. It binds to HEPARIN, which potentiates its biological activity and protects it from proteolysis. The growth factor is an extremely potent inducer of DNA synthesis in a variety of cell types from mesoderm and neuroectoderm lineages, and also has chemotactic and mitogenic activities. It was originally named acidic fibroblast growth factor based upon its chemical properties and to distinguish it from basic fibroblast growth factor (FIBROBLAST GROWTH FACTOR 2).
The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.
Established cell cultures that have the potential to propagate indefinitely.
A fibroblast growth factor receptor with specificity for FIBROBLAST GROWTH FACTORS; HEPARAN SULFATE PROTEOGLYCAN; and NEURONAL CELL ADHESION MOLECULES. Several variants of the receptor exist due to multiple ALTERNATIVE SPLICING of its mRNA. Fibroblast growth factor receptor 1 is a tyrosine kinase that transmits signals through the MAP KINASE SIGNALING SYSTEM.
A fibroblast growth factor receptor that is found in two isoforms. One receptor isoform is found in the MESENCHYME and is activated by FIBROBLAST GROWTH FACTOR 2. A second isoform of fibroblast growth factor receptor 2 is found mainly in EPITHELIAL CELLS and is activated by FIBROBLAST GROWTH FACTOR 7 and FIBROBLAST GROWTH FACTOR 10. Mutation of the gene for fibroblast growth factor receptor 2 can result in craniosynostotic syndromes (e.g., APERT SYNDROME; and CROUZON SYNDROME).
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
A fibroblast growth factor receptor that regulates CHONDROCYTE growth and CELL DIFFERENTIATION. Mutations in the gene for fibroblast growth factor receptor 3 have been associated with ACHONDROPLASIA; THANATOPHORIC DYSPLASIA and NEOPLASTIC CELL TRANSFORMATION.
A layer of vascularized connective tissue underneath the EPIDERMIS. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are SWEAT GLANDS; HAIR FOLLICLES; and SEBACEOUS GLANDS.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A sharply elevated, irregularly shaped, progressively enlarging scar resulting from formation of excessive amounts of collagen in the dermis during connective tissue repair. It is differentiated from a hypertrophic scar (CICATRIX, HYPERTROPHIC) in that the former does not spread to surrounding tissues.
A fibroblast growth factor that is a mitogen for KERATINOCYTES. It activates FIBROBLAST GROWTH FACTOR RECEPTOR 2B and is involved in LUNG and limb development.
Restoration of integrity to traumatized tissue.
A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.
A fibroblast growth factor that is a specific mitogen for EPITHELIAL CELLS. It binds a complex of HEPARAN SULFATE and FIBROBLAST GROWTH FACTOR RECEPTOR 2B.
The most common form of fibrillar collagen. It is a major constituent of bone (BONE AND BONES) and SKIN and consists of a heterotrimer of two alpha1(I) and one alpha2(I) chains.
Signal molecules that are involved in the control of cell growth and differentiation.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.
A continuous cell line of high contact-inhibition established from NIH Swiss mouse embryo cultures. The cells are useful for DNA transfection and transformation studies. (From ATCC [Internet]. Virginia: American Type Culture Collection; c2002 [cited 2002 Sept 26]. Available from
The decrease in the cell's ability to proliferate with the passing of time. Each cell is programmed for a certain number of cell divisions and at the end of that time proliferation halts. The cell enters a quiescent state after which it experiences CELL DEATH via the process of APOPTOSIS.
Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins.
A fibroblast growth factor receptor that is mainly expressed in LUNG; KIDNEY; PANCREAS; and SPLEEN. It also plays an important role in SKELETAL MUSCLE development and can contribute to NEOPLASTIC CELL TRANSFORMATION.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS.
Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Mitogenic peptide growth hormone carried in the alpha-granules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication.
A fibroblast growth factor that may play a role in regulation of HAIR FOLLICLE phenotype. Spontaneous mutation of the gene for this protein results in a strain of MICE with abnormally long hair, referred to as angora mice.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes SYNOVIAL FLUID.
A chronic multi-system disorder of CONNECTIVE TISSUE. It is characterized by SCLEROSIS in the SKIN, the LUNGS, the HEART, the GASTROINTESTINAL TRACT, the KIDNEYS, and the MUSCULOSKELETAL SYSTEM. Other important features include diseased small BLOOD VESSELS and AUTOANTIBODIES. The disorder is named for its most prominent feature (hard skin), and classified into subsets by the extent of skin thickening: LIMITED SCLERODERMA and DIFFUSE SCLERODERMA.
The rate dynamics in chemical or physical systems.
A HEPARIN binding fibroblast growth factor that may play a role in LIMB BUDS development.
Adherence of cells to surfaces or to other cells.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.
A subtype of transforming growth factor beta that is synthesized by a wide variety of cells. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta 1 and TGF-beta1 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor. Defects in the gene that encodes TGF-beta1 are the cause of CAMURATI-ENGELMANN SYNDROME.
Culture media containing biologically active components obtained from previously cultured cells or tissues that have released into the media substances affecting certain cell functions (e.g., growth, lysis).
Proteins prepared by recombinant DNA technology.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
A member of the metalloproteinase family of enzymes that is principally responsible for cleaving FIBRILLAR COLLAGEN. It can degrade interstitial collagens, types I, II and III.
Elements of limited time intervals, contributing to particular results or situations.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
An inheritable change in cells manifested by changes in cell division and growth and alterations in cell surface properties. It is induced by infection with a transforming virus.
Methods for maintaining or growing CELLS in vitro.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Tissue that supports and binds other tissues. It consists of CONNECTIVE TISSUE CELLS embedded in a large amount of EXTRACELLULAR MATRIX.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.
A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal and carboxyl-terminal ends of the polypeptide chains.
A process in which normal lung tissues are progressively replaced by FIBROBLASTS and COLLAGEN causing an irreversible loss of the ability to transfer oxygen into the bloodstream via PULMONARY ALVEOLI. Patients show progressive DYSPNEA finally resulting in death.
Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP.
A fibroblast growth factor that preferentially activates FIBROBLAST GROWTH FACTOR RECEPTOR 4. It was initially identified as an androgen-induced growth factor and plays a role in regulating growth of human BREAST NEOPLASMS and PROSTATIC NEOPLASMS.
Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere.
Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
A naturally occurring phenomenon where terminally differentiated cells dedifferentiate to the point where they can switch CELL LINEAGES. The cells then differentiate into other cell types.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
Substances that stimulate mitosis and lymphocyte transformation. They include not only substances associated with LECTINS, but also substances from streptococci (associated with streptolysin S) and from strains of alpha-toxin-producing staphylococci. (Stedman, 25th ed)
Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as AGAR or GELATIN.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
A cultured line of C3H mouse FIBROBLASTS that do not adhere to one another and do not express CADHERINS.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
Cellular signaling in which a factor secreted by a cell affects other cells in the local environment. This term is often used to denote the action of INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS on surrounding cells.
Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., COLLAGEN; ELASTIN; FIBRONECTINS; and LAMININ).
A metalloproteinase which degrades helical regions of native collagen to small fragments. Preferred cleavage is -Gly in the sequence -Pro-Xaa-Gly-Pro-. Six forms (or 2 classes) have been isolated from Clostridium histolyticum that are immunologically cross-reactive but possess different sequences and different specificities. Other variants have been isolated from Bacillus cereus, Empedobacter collagenolyticum, Pseudomonas marinoglutinosa, and species of Vibrio and Streptomyces. EC
The sum of the weight of all the atoms in a molecule.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.
A group of inherited metabolic diseases characterized by the accumulation of excessive amounts of acid mucopolysaccharides, sphingolipids, and/or glycolipids in visceral and mesenchymal cells. Abnormal amounts of sphingolipids or glycolipids are present in neural tissue. INTELLECTUAL DISABILITY and skeletal changes, most notably dysostosis multiplex, occur frequently. (From Joynt, Clinical Neurology, 1992, Ch56, pp36-7)
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
A CCN protein family member that regulates a variety of extracellular functions including CELL ADHESION; CELL MIGRATION; and EXTRACELLULAR MATRIX synthesis. It is found in hypertrophic CHONDROCYTES where it may play a role in CHONDROGENESIS and endochondral ossification.
Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell.
The functions of the skin in the human and animal body. It includes the pigmentation of the skin.
A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured. Such rupture is supposed to be under metabolic (hormonal) control. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
Transport proteins that carry specific substances in the blood or across cell membranes.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
Glycoproteins which have a very high polysaccharide content.
CULTURE MEDIA free of serum proteins but including the minimal essential substances required for cell growth. This type of medium avoids the presence of extraneous substances that may affect cell proliferation or unwanted activation of cells.
A group of cells that includes FIBROBLASTS, cartilage cells, ADIPOCYTES, smooth muscle cells, and bone cells.
Enzymes that catalyze the degradation of collagen by acting on the peptide bonds.
Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquefies; the resulting colloid is called a sol.
Bony cavity that holds the eyeball and its associated tissues and appendages.
Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.
The transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous CORNEAL EPITHELIUM; BOWMAN MEMBRANE; CORNEAL STROMA; DESCEMET MEMBRANE; and mesenchymal CORNEAL ENDOTHELIUM. It serves as the first refracting medium of the eye. It is structurally continuous with the SCLERA, avascular, receiving its nourishment by permeation through spaces between the lamellae, and is innervated by the ophthalmic division of the TRIGEMINAL NERVE via the ciliary nerves and those of the surrounding conjunctiva which together form plexuses. (Cline et al., Dictionary of Visual Science, 4th ed)
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or N-acetylgalactosamine.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.
A cell line derived from cultured tumor cells.
The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.
A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
A natural high-viscosity mucopolysaccharide with alternating beta (1-3) glucuronide and beta (1-4) glucosaminidic bonds. It is found in the UMBILICAL CORD, in VITREOUS BODY and in SYNOVIAL FLUID. A high urinary level is found in PROGERIA.
The chromosomal constitution of cells, in which each type of CHROMOSOME is represented twice. Symbol: 2N or 2X.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
Group of alpharetroviruses (ALPHARETROVIRUS) producing sarcomata and other tumors in chickens and other fowl and also in pigeons, ducks, and RATS.
The unborn young of a viviparous mammal, in the postembryonic period, after the major structures have been outlined. In humans, the unborn young from the end of the eighth week after CONCEPTION until BIRTH, as distinguished from the earlier EMBRYO, MAMMALIAN.
A heteropolysaccharide that is similar in structure to HEPARIN. It accumulates in individuals with MUCOPOLYSACCHARIDOSIS.
Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein.
Arrest of cell locomotion or cell division when two cells come into contact.
An extracellular endopeptidase of vertebrate tissues similar to MATRIX METALLOPROTEINASE 1. It digests PROTEOGLYCAN; FIBRONECTIN; COLLAGEN types III, IV, V, and IX, and activates procollagenase. (Enzyme Nomenclature, 1992)
The fibrous tissue that replaces normal tissue during the process of WOUND HEALING.
Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors.
The number of CELLS of a specific kind, usually measured per unit volume or area of sample.
A fibrillar collagen consisting of three identical alpha1(III) chains that is widely distributed in many tissues containing COLLAGEN TYPE I. It is particularly abundant in BLOOD VESSELS and may play a role in tissues with elastic characteristics.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of "v-" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix "c-" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
The process by which a DNA molecule is duplicated.
A receptor-regulated smad protein that undergoes PHOSPHORYLATION by ACTIVIN RECEPTORS, TYPE I. Activated Smad3 can bind directly to DNA, and it regulates TRANSFORMING GROWTH FACTOR BETA and ACTIVIN signaling.
A class of enzymes that catalyzes the degradation of gelatin by acting on the peptide bonds. EC 3.4.24.-.
Family of RNA viruses that infects birds and mammals and encodes the enzyme reverse transcriptase. The family contains seven genera: DELTARETROVIRUS; LENTIVIRUS; RETROVIRUSES TYPE B, MAMMALIAN; ALPHARETROVIRUS; GAMMARETROVIRUS; RETROVIRUSES TYPE D; and SPUMAVIRUS. A key feature of retrovirus biology is the synthesis of a DNA copy of the genome which is integrated into cellular DNA. After integration it is sometimes not expressed but maintained in a latent state (PROVIRUSES).
A fibroblast growth factor that is expressed primarily during development.
The double-layered skin fold that covers the GLANS PENIS, the head of the penis.
A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.
Cellular DNA-binding proteins encoded by the sis gene (GENES, SIS). c-sis proteins make up the B chain of PLATELET-DERIVED GROWTH FACTOR. Overexpression of c-sis causes tumorigenesis.
Any cell, other than a ZYGOTE, that contains elements (such as NUCLEI and CYTOPLASM) from two or more different cells, usually produced by artificial CELL FUSION.
A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS.
The fibrous CONNECTIVE TISSUE surrounding the TOOTH ROOT, separating it from and attaching it to the alveolar bone (ALVEOLAR PROCESS).
Methods of maintaining or growing biological materials in controlled laboratory conditions. These include the cultures of CELLS; TISSUES; organs; or embryo in vitro. Both animal and plant tissues may be cultured by a variety of methods. Cultures may derive from normal or abnormal tissues, and consist of a single cell type or mixed cell types.
The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
The quality of surface form or outline of CELLS.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
A cell line established in 1962 from disaggregated Swiss albino mouse embryos. This fibroblast cell line is extremely popular in research.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
A species of POLYOMAVIRUS originally isolated from Rhesus monkey kidney tissue. It produces malignancy in human and newborn hamster kidney cell cultures.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
The development of new BLOOD VESSELS during the restoration of BLOOD CIRCULATION during the healing process.
A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.
Retrovirus-associated DNA sequences (src) originally isolated from the Rous sarcoma virus (RSV). The proto-oncogene src (c-src) codes for a protein that is a member of the tyrosine kinase family and was the first proto-oncogene identified in the human genome. The human c-src gene is located at 20q12-13 on the long arm of chromosome 20.
Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.
A secreted endopeptidase homologous with INTERSTITIAL COLLAGENASE, but which possesses an additional fibronectin-like domain.
A vascular connective tissue formed on the surface of a healing wound, ulcer, or inflamed tissue. It consists of new capillaries and an infiltrate containing lymphoid cells, macrophages, and plasma cells.
A genus of the family HERPESVIRIDAE, subfamily BETAHERPESVIRINAE, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS.

Glycopeptides from the surgace of human neuroblastoma cells. (1/31038)

Glycopeptides suggesting a complex oligosaccharide composition are present on the surface of cells from human neuroblastoma tumors and several cell lines derived from the tumors. The glycopeptides, labeled with radioactive L-fucose, were removed from the cell surface with trypsin, digested with Pronase, and examined by chromatography on Sephadex G-50. Human skin fibroblasts, brain cells, and a fibroblast line derived from neuroblastoma tumor tissue show less complex glycopeptides. Although some differences exist between the cell lines and the primary tumor cells, the similarities between these human tumors and animal tumors examined previously are striking.  (+info)

Stimulation of thymidine uptake and cell proliferation in mouse embryo fibroblasts by conditioned medium from mammary cells in culture. (2/31038)

Undialyzed conditioned medium from several cell culture sources did not stimulate thymidine incorporation or cell overgrowth in quiescent, density-inhibited mouse embryo fibroblast cells. However, dialyzed conditioned medium (DCM) from clonal mouse mammary cell lines MCG-V14, MCG-T14, MCG-T10; HeLa cells; primary mouse adenocarcinoma cells; and BALB/c normal mouse mammary epithelial cells promoted growth in quiescent fibroblasts. The amount of growth-promoting activity produced per cell varied from 24% (HeLa) to 213% (MCG-V14) of the activity produced by primary tumor cells. The production of growth-promoting activity was not unique to tumor-derived cells or cells of high tumorigenicity. The amount of growth-promoting activity produced per cell in the active cultures was not correlated with any of the following: tumorigenicity, growth rat, cell density achieved at saturation, cell type, or species of cell origin. It is concluded that transformed and non-transformed cells of diverse origin, cell type, and tumorigenicity can produce growth factors in culture. The growth-promoting potential of the active media from primary tumor cultures accumulated with time of contact with cells and was too great to be accounted for entirely by the removal of low-molecular-weight inhibitors by dialysis. The results are consistent with the hypothesis that conditioned medium from the active cultures contained a dialyzable, growth-promoting activity. Different cell lines exhibited differential sensitivity to tumor cell DCM and fetal bovine serum. Furthermore, quiescent fibroblasts were stimulated by primary tumor cell DCM in the presence of saturating concentrations of fetal bovine serum. These observations support the notion that the active growth-promoting principle in primary tumor cell DCM may not be a serum factor(s).  (+info)

Lymphocyte proliferation inhibitory factor (PIF) in alcoholic liver disease. (3/31038)

Lymphocyte proliferation inhibitory factor (PIF) was determined in the supernatants of PHA-stimulated lymphocytes from patients with alcoholic liver disease. PIF was assayed by determining inhibition of DNA synthesis in WI-38 human lung fibroblasts. A two-fold greater inhibition in thymidine incorporation into DNA by lung fibroblasts was observed in supernatants of PHA stimulated lymphocytes from patients with alcoholic hepatitis or active Laennec's cirrhosis as compared with that found in control subjects or patients with fatty liver. It is suggested that decreased liver cell regeneration seen in some patients with alcoholic hepatitis may be due to increased elaboration of PIF.  (+info)

CAR-dependent and CAR-independent pathways of adenovirus vector-mediated gene transfer and expression in human fibroblasts. (4/31038)

Primary fibroblasts are not efficiently transduced by subgroup C adenovirus (Ad) vectors because they express low levels of the high-affinity Coxsackie virus and adenovirus receptor (CAR). In the present study, we have used primary human dermal fibroblasts as a model to explore strategies by which Ad vectors can be designed to enter cells deficient in CAR. Using an Ad vector expressing the human CAR cDNA (AdCAR) at high multiplicity of infection, primary fibroblasts were converted from being CAR deficient to CAR sufficient. Efficiency of subsequent gene transfer by standard Ad5-based vectors and Ad5-based vectors with alterations in penton and fiber was evaluated. Marked enhancement of binding and transgene expression by standard Ad5 vectors was achieved in CAR-sufficient fibroblasts. Expression by AdDeltaRGDbetagal, an Ad5-based vector lacking the arginine-glycine-aspartate (RGD) alphaV integrin recognition site from its penton base, was achieved in CAR-sufficient, but not CAR-deficient, cells. Fiber-altered Ad5-based vectors, including (a) AdF(pK7)betagal (bearing seven lysines on the end of fiber) (b) AdF(RGD)betagal (bearing a high-affinity RGD sequence on the end of fiber), and (c) AdF9sK betagal (bearing a short fiber and Ad9 knob), demonstrated enhanced gene transfer in CAR-deficient fibroblasts, with no further enhancement in CAR-sufficient fibroblasts. Together, these observations demonstrate that CAR deficiency on Ad targets can be circumvented either by supplying CAR or by modifying the Ad fiber to bind to other cell-surface receptors.  (+info)

Concomitant activation of pathways downstream of Grb2 and PI 3-kinase is required for MET-mediated metastasis. (5/31038)

The Met tyrosine kinase - the HGF receptor - induces cell transformation and metastasis when constitutively activated. Met signaling is mediated by phosphorylation of two carboxy-terminal tyrosines which act as docking sites for a number of SH2-containing molecules. These include Grb2 and p85 which couple the receptor, respectively, with Ras and PI 3-kinase. We previously showed that a Met mutant designed to obtain preferential coupling with Grb2 (Met2xGrb2) is permissive for motility, increases transformation, but - surprisingly - is impaired in causing invasion and metastasis. In this work we used Met mutants optimized for binding either p85 alone (Met2xPI3K) or p85 and Grb2 (MetPI3K/Grb2) to evaluate the relative importance of Ras and PI 3-kinase as downstream effectors of Met. Met2xPI3K was competent in eliciting motility, but not transformation, invasion, or metastasis. Conversely, MetP13K/Grb2 induced motility, transformation, invasion and metastasis as efficiently as wild type Met. Furthermore, the expression of constitutively active PI 3-kinase in cells transformed by the Met2xGrb2 mutant, fully rescued their ability to invade and metastasize. These data point to a central role for PI 3-kinase in Met-mediated invasiveness, and indicate that simultaneous activation of Ras and PI 3-kinase is required to unleash the Met metastatic potential.  (+info)

Differential stability of the DNA-activated protein kinase catalytic subunit mRNA in human glioma cells. (6/31038)

DNA-dependent protein kinase (DNA-PK) functions in double-strand break repair and immunoglobulin [V(D)J] recombination. We previously established a radiation-sensitive human cell line, M059J, derived from a malignant glioma, which lacks the catalytic subunit (DNA-PKcs) of the DNA-PK multiprotein complex. Although previous Northern blot analysis failed to detect the DNA-PKcs transcript in these cells, we show here through quantitative studies that the transcript is present, albeit at greatly reduced (approximately 20x) levels. Sequencing revealed no genetic alteration in either the promoter region, the kinase domain, or the 3' untranslated region of the DNA-PKcs gene to account for the reduced transcript levels. Nuclear run-on transcription assays indicated that the rate of DNA-PKcs transcription in M059J and DNA-PKcs proficient cell lines was similar, but the stability of the DNA-PKcs message in the M059J cell line was drastically (approximately 20x) reduced. Furthermore, M059J cells lack an alternately spliced DNA-PKcs transcript that accounts for a minor (5-20%) proportion of the DNA-PKcs message in all other cell lines tested. Thus, alterations in DNA-PKcs mRNA stability and/or the lack of the alternate mRNA may result in the loss of DNA-PKcs activity. This finding has important implications as DNA-PKcs activity is essential to cells repairing damage induced by radiation or radiomimetric agents.  (+info)

Signals from the Ras, Rac, and Rho GTPases converge on the Pak protein kinase in Rat-1 fibroblasts. (7/31038)

Ras plays a key role in regulating cellular proliferation, differentiation, and transformation. Raf is the major effector of Ras in the Ras > Raf > Mek > extracellular signal-activated kinase (ERK) cascade. A second effector is phosphoinositide 3-OH kinase (PI 3-kinase), which, in turn, activates the small G protein Rac. Rac also has multiple effectors, one of which is the serine threonine kinase Pak (p65(Pak)). Here we show that Ras, but not Raf, activates Pak1 in cotransfection assays of Rat-1 cells but not NIH 3T3 cells. We tested agents that activate or block specific components downstream of Ras and demonstrate a Ras > PI 3-kinase > Rac/Cdc42 > Pak signal. Although these studies suggest that the signal from Ras through PI 3-kinase is sufficient to activate Pak, additional studies suggested that other effectors contribute to Pak activation. RasV12S35 and RasV12G37, two effector mutant proteins which fail to activate PI 3-kinase, did not activate Pak when tested alone but activated Pak when they were cotransfected. Similarly, RacV12H40, an effector mutant that does not bind Pak, and Rho both cooperated with Raf to activate Pak. A dominant negative Rho mutant also inhibited Ras activation of Pak. All combinations of Rac/Raf and Ras/Raf and Rho/Raf effector mutants that transform cells cooperatively stimulated ERK. Cooperation was Pak dependent, since all combinations were inhibited by kinase-deficient Pak mutants in both transformation assays and ERK activation assays. These data suggest that other Ras effectors can collaborate with PI 3-kinase and with each other to activate Pak. Furthermore, the strong correlation between Pak activation and cooperative transformation suggests that Pak activation is necessary, although not sufficient, for cooperative transformation of Rat-1 fibroblasts by Ras, Rac, and Rho.  (+info)

Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. (8/31038)

The irreversible G1 arrest in senescent human diploid fibroblasts is probably caused by inactivation of the G1 cyclin-cyclin-dependent kinase (Cdk) complexes responsible for phosphorylation of the retinoblastoma protein (pRb). We show that the Cdk inhibitor p21(Sdi1,Cip1,Waf1), which accumulates progressively in aging cells, binds to and inactivates all cyclin E-Cdk2 complexes in senescent cells, whereas in young cells only p21-free Cdk2 complexes are active. Furthermore, the senescent-cell-cycle arrest occurs prior to the accumulation of the Cdk4-Cdk6 inhibitor p16(Ink4a), suggesting that p21 may be sufficient for this event. Accordingly, cyclin D1-associated phosphorylation of pRb at Ser-780 is lacking even in newly senescent fibroblasts that have a low amount of p16. Instead, the cyclin D1-Cdk4 and cyclin D1-Cdk6 complexes in these cells are associated with an increased amount of p21, suggesting that p21 may be responsible for inactivation of both cyclin E- and cyclin D1-associated kinase activity at the early stage of senescence. Moreover, even in the late stage of senescence when p16 is high, cyclin D1-Cdk4 complexes are persistent, albeit reduced by +info)

Rat ES cells were derived using 3I medium from E4.5 blastocysts. Rat embryonic fibroblast cells were derived form E14.5 embryos. To analyze the mechanism under the selfrenewal of rat ES cells, microarrays were used for the genome wide analysis of gene expressoin profiles in rat ES cells. Rat embryonic fibroblast cells and mouse ES cells were tested at same time as control. Our results from clustering analysis demonstrated that the gene expression profile of rat ES cells resembles mouse ES cells, but not REFs. Keyword: 3I medium; rat embryonic stem cells; mouse ES cells; rat embryonic fibroblast cells Rat ES cells were cultured in 3I medium; rat embryonic fibroblast cells were derived and cultured GMEM/10% FBS; mouse ES cells (C57/BL6)were cultured in GMEM/10% FBS added LIF and feeder cells were removed before RNA extraction. Three replicates each.
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TY - JOUR. T1 - Retinoic acid restores normal growth control to a transformed mouse embryo fibroblast cell line. AU - Levine, Alan E.. AU - Crandall, Craig A.. AU - Brattain, Diane. AU - Chakrabarty, Subhas. AU - Brattain, Michael G.. PY - 1986/10. Y1 - 1986/10. N2 - The effects of retinoic acid on a transformed mouse embryo fibroblast cell line (AKR-MCA) were examined. Treatment with retinoic acid restored a non-transformed phenotype to this transformed cell line in a dose dependent manner. Retinoic acid (RA) treated AKR-MCA cells showed a non-transformed morphology, a slower growth rate, and did not grow with anchorage independence. A 38,000 Da protein was phosphorylated to a high degree in the AKR-MCA transformed cell line compared to the non-transformed AKR-2B cell line. RA treatment greatly reduced the level of phosphorylation of this protein in AKR-MCA cells. Growth arrested AKR-MCA cells showed a mitogenic response to nutrient replenishment, but not to epidermal growth factor (EGF). ...
Murine studies have shown that immunologic targeting of the tumor vasculature, a key element of the tumor stroma, can lead to protective immunity in the absence of significant pathology. In the current study, we expand the scope of stroma-targeted immunotherapy to antigens expressed in tumor-associated fibroblasts, the predominant component of the stroma in most types of cancer. Mice were immunized against fibroblast activation protein (FAP), a product up-regulated in tumor-associated fibroblasts, using dendritic cells transfected with FAP mRNA. Using melanoma, carcinoma, and lymphoma models, we show that tumor growth was inhibited in tumor-bearing mice vaccinated against FAP and that the magnitude of the antitumor response was comparable to that of vaccination against tumor cell-expressed antigens. Both s.c. implanted tumors and lung metastases were susceptible to anti-FAP immunotherapy. The antitumor response could be further enhanced by augmenting the CD4+ T-cell arm of the anti-FAP immune ...
It is well accepted that there is an increase in the number of fibroblasts in the airways of patients with asthma that correlates with thickness of lamina reticularis and disease severity. Moreover, fibroblast activation and differentiation to myofibroblasts are also evident [1-4].. In the present study, we aimed to investigate the in vitro effect of glucocorticosteroids and short-acting β2-agonists widely used as first-line antiasthmatic drugs on human lung fibroblast proliferation and IL-6 production. We specifically choose to evaluate fibroblast proliferation because this is the first hallmark of fibrosis taking place. IL-6 was selected among a plethora of proinflammatory profibrotic cytokines produced by the fibroblast[22] that mainly influences the inflammatory response [23, 24].. We found that dexamethasone and salbutamol alone and in combination increase both human fetal lung and human bronchial fibroblast proliferation. Moreover, we demonstrate for the first time that when the ...
Title: Genetic characterization of skin fibroblast cell lines by DNA fingerprinting. Authors: NK Nagpal, BK Beniwal, GC Gahlot and SC Gupta. Source: Ruminant Science (2016)-5(2):149-158.. Cite this reference as: Nagpal NK, Beniwal BK, Gahlot GC and Gupta SC (2016). Genetic characterization of skin fibroblast cell lines by DNA fingerprinting. Ruminant Science 5(2):149-158.. Abstract. Present study was carried out for genetic characterization of Bhadawari buffalo skin fibroblast cell lines using ten microsatellite primers. The primary cells explants from tissue of six cell lines MF-22, MF-37 and MF-82 (females) and MM-31, MM-32 and MM-79 (males) collected from 6-8 months old calves of Bhadawari buffalo breed were employed for development of cell lines. To establish the integrity of cell line which may have lost due to improper passaging, sharing of cultural media or inaccurate labeling, DNA fingerprinting was exercised. The PCR and denaturing sequence gel electrophoresis were carried out for ...
Title: Genetic characterization of skin fibroblast cell lines by DNA fingerprinting. Authors: NK Nagpal, BK Beniwal, GC Gahlot and SC Gupta. Source: Ruminant Science (2016)-5(2):149-158.. Cite this reference as: Nagpal NK, Beniwal BK, Gahlot GC and Gupta SC (2016). Genetic characterization of skin fibroblast cell lines by DNA fingerprinting. Ruminant Science 5(2):149-158.. Abstract. Present study was carried out for genetic characterization of Bhadawari buffalo skin fibroblast cell lines using ten microsatellite primers. The primary cells explants from tissue of six cell lines MF-22, MF-37 and MF-82 (females) and MM-31, MM-32 and MM-79 (males) collected from 6-8 months old calves of Bhadawari buffalo breed were employed for development of cell lines. To establish the integrity of cell line which may have lost due to improper passaging, sharing of cultural media or inaccurate labeling, DNA fingerprinting was exercised. The PCR and denaturing sequence gel electrophoresis were carried out for ...
TY - JOUR. T1 - PFG acted as an inducer of premature senescence in TIG-1 normal diploid fibroblast and an inhibitor of mitosis in the HeLa cells. AU - Huang, Ying. AU - Ohno, Osamu. AU - Miyamoto, Kenji. PY - 2019/6/1. Y1 - 2019/6/1. N2 - Our previous work has reported an anti-proliferative compound from moutan cortex, paeoniflorigenone which can induce cancer-selective apoptosis. However, its anti-proliferative mechanism is still unknown. According to morphology changes (hypertrophy and flattening), we hypothesized that PFG can induce senescence or inhibit cell mitosis. Here we show that PFG can induce cellular senescence, evidenced by the expression of senescence-associated β-galactosidase, G0/G1 cell cycle arrest and permanent loss of proliferative ability, in normal TIG-1 diploid fibroblast but not cancerous HeLa cells. In cancerous HeLa cells, PFG inhibited proliferation by inducing S and G2/M cell cycle arrest and mitosis inhibition. DNA damage response was activated by PFG, interestingly ...
Fibroblasts play important roles in several cancers. It was hypothesized that cholangiocarcinoma (CCA)-associated fibroblasts (Cfs) differ from non-tumorigenic liver fibroblasts (Lfs) in their gene expression profiles resulting in the capability to promote cancer. Periostin (PN) is a multi-functional protein and has emerged as a promising marker for tumor progression. The role of PN in CCA, however, has not yet been explored. In this study, the gene expression profile of Cfs in comparison to Lfs was performed using oligonucleotide microarrays. The common- and unique-expressed genes in Cfs and the promising roles in cancer promotion and progression were determined. PN was markedly over-expressed in Cfs confirmed by real time RT-PCR and western blot analysis. Immunohistochemistry examination of a number of patients with intrahepatic CCA showed the expression of PN solely in stromal fibroblasts, but was expressed neither in cancer cells nor immune cells. Low to no expression of PN was observed in tissues
In our laboratory, recent single cell electrophysiologic studies have demonstrated the absence of voltage-gated Ca2+ channels in human cardiac fibroblasts. The more positive membrane potential found in these cells suggests that Ca2+ entry occurs through a different mechanism. We hypothesized that non-voltage-gated Ca2+-permeable TRP channels are responsible for Ca2+ entry in human cardiac fibroblasts. With informed consent, right atrial biopsies were obtained from patients undergoing cardiac surgery (n=4:.3M, 1F; mean age 65±8 yrs, EF 63±5%, LVEDP 24±4 mm Hg). Fibroblasts were dissociated and cultured for 7 to 10 days. We found that TRPC1, TRPC4, TRPC6, TRPV4, TRPV5, TRPV6, TRPM4 and TRPM7 were detectable at message levels by RT-PCR. Functional expression of these channels was evaluated by patch-clamp technique. An outward rectifying current with typical I-V relation of TRPM7 was readily recorded in the fibroblasts. The averaged current density was 14.5±0.8 pA/pF (mean±SEM, n=60 from four ...
TY - JOUR. T1 - Protective effect of resveratrol against caspase 3 activation in primary mouse fibroblasts. AU - Ulakcsai, Zsófia. AU - Bagaméry, Fruzsina. AU - Vincze, István. AU - Szöko, Éva. AU - Tábi, Tamás. PY - 2015/1/1. Y1 - 2015/1/1. N2 - Aim: To study the effect of resveratrol on survival and caspase 3 activation in non-transformed cells after serum deprivation. Methods: Apoptosis was induced by serum deprivation in primary mouse embryonic fibroblasts. Caspase 3 activation and lactate dehydrogenase release were assayed as cell viability measure by using their fluorogenic substrates. The involvement of PI3K, ERK, JNK, p38, and SIRT1 signaling pathways was also examined. Results: Serum deprivation of primary fibroblasts induced significant activation of caspase 3 within 3 hours and reduced cell viability after 24 hours. Resveratrol dose-dependently prevented caspase activation and improved cell viability with 50% inhibitory concentration (IC50) = 66.3 ± 13.81 μM. It also reduced ...
TY - JOUR. T1 - Altered transcriptome signature of phenotypically normal skin fibroblasts heterozygous for CDKN2A in familial melanoma. T2 - Relevance to early intervention. AU - Fan, Meiyun. AU - Pfeffer, Susan R.. AU - Lynch, Henry T.. AU - Cassidy, Pamela. AU - Leachman, Sancy. AU - Pfeffer, Lawrence M.. AU - Kopelovich, Levy. PY - 2013. Y1 - 2013. N2 - Familial melanoma (FM) is a dominantly heritable cancer that is associated with mutations in the tumor suppressor CDKN2A/p16. In FM, a single inherited hit occurs in every somatic cell, enabling interrogation of cultured normal skin fibroblasts (SFs) from FM gene carriers as surrogates for the cell of tumor origin, namely the melanocyte.We compared the gene expression profile of SFs from FM individuals with two distinct CDKN2A/p16 mutations (V126D-p16 and R87P-p16) with the gene expression profile of SFs from age-matched individuals without p16 mutations and with no family history of melanoma. We show an altered transcriptome signature in ...
p,Fibroblasts play a major role in heart physiology. They are at the origin of the extracellular matrix renewal and production of various paracrine and autocrine factors. In pathological conditions, fibroblasts proliferate, migrate and differentiate into myofibroblasts leading to cardiac fibrosis. This differentiated status is associated with changes in expression profile leading to neo-expression of proteins such as ionic channels. The present study investigates further electrophysiological changes associated with fibroblast differentiation focusing on the activity of voltage-gated sodium channels in human atrial fibroblasts and myofibroblasts. Using the patch clamp technique we show that human atrial myofibroblasts display a fast inward voltage gated sodium current with a density of 13.28 ± 2.88 pA pF(-1) whereas no current was detectable in non-differentiated fibroblasts. Quantitative RT-PCR reveals a large amount of transcripts encoding the Na(v)1.5 α-subunit with a fourfold increased ...
Human fibroblasts include: bladder, cardiac, dermal, gingival, lung-airway, prostate, scleral, uterine, and vas deferens.. Lifeline® normal Human Fibroblasts provide an ideal cell system to study wound healing, toxicology, cancer, or basic cell biology in various organs including skin, lung, bladder, and the reproductive systems. Our normal Human Fibroblasts can also be used for drug screening, drug development, and genome editing applications. Additionally, our fibroblast lines are ideal for establishing serum free human feeder layers for human embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and other cell culture applications requiring feeder layers.. Human Dermal Fibroblasts (Adult or Neonatal) and Xeno-Free Human Dermal Fibroblasts are cryopreserved as primary cells ...
Administration of selected concentrations of ebselen and N-acetyl cysteine have been proven to display an antioxidant potential based on their effect on markers of T cell integrity and function in human peripheral blood mononuclear cells and CD4+ T cell clones. Here we assessed the impact of various antioxidant concentrations on replicative aging of primary human fibroblast strains derived from embryonic lung (MRC-5) and foreskin (HFF). None of the antioxidant concentrations affected the cumulative population doublings, levels of oxidative DNA damage, intracellular GSH:GSSG ratio, potency of heat shock responses and the induction of senescence in both fibroblast strains. Our results showed no effect of both antioxidants on primary fibroblast strains and reveal their cell type specific antioxidant potential.
TY - JOUR. T1 - The connexin mimetic peptide Gap27 increases human dermal fibroblast migration in hyperglycemic and hyperinsulinemic conditions in vitro. AU - Wright, Catherine. AU - Pollok, Simone AU - Flint, David J.. AU - Brandner, Johanna M.. AU - Martin, Patricia. N1 - publisher version of article not permitted for display in repositories (ET 18-10-13). PY - 2012/1. Y1 - 2012/1. N2 - Significant increases in skin wound healing rates occur by reducing connexin-mediated communication (CMC). Gap27, a connexin (Cx) mimetic peptide targeted to the second extracellular loop of Cx43, which inhibits CMC, increases migration of human keratinocytes and dermal fibroblasts. To examine the efficacy of Gap27 in a hyperglycemic and hyperinsulinemic in vitro environment, cell migration, gap junction, and Cx hemichannel functionality and cell-substrate adhesion assays were performed on human dermal fibroblasts and diabetic fibroblast and keratinocytes. AB - Significant increases in skin wound healing rates ...
Human fibroblasts can express and transport both PC-I aggregates and VSVG through the Golgi complex. Human fibroblasts were stimulated to synthesize PC-I and in
Applied mechanical forces, such as those resulting from fluid flow, trigger cells to change their functional behavior or phenotype. However, there is little known about how fluid flow affects fibroblasts. The hypothesis of this thesis is that dermal fibroblasts undergo significant changes of expression of differentiation genes after exposure to fluid flow (or shear stress). To test the hypothesis, human dermal fibroblasts were exposed to laminar steady fluid flow for 20 and 40 hours and RNA was collected for microarray analysis. Gene expression data was processed using gene network analysis, pathway analysis, and gene functional analysis with comparison to data from publicly available data sets. Additional treatment with PI3K/mTOR pathway inhibitor, PI-103, was performed to evaluate pathway involvement in flow modulation of gene expression. Results from overall transcription analysis demonstrated that fluid flow modulated many genes in fibroblasts including those related to differentiation, ...
Helen There is a marker called prolyl-4-hydroxylase that is supposed to react with fibroblasts. Its from Acris cat number AF5110-1. The antibody is a mouse anti-rat. It is supposed to work in FFPE material. I just received it and have not had a change to start working on it, but I can update as soon as I start working with it. Liz Elizabeth A. Chlipala, BS, HTL(ASCP)QIHC Manager Premier Laboratory, LLC P.O. Box 18592 Boulder, Colorado 80308 Office: (303) 735-5001 Fax: (303) 735-3540 [email protected] Ship to Address: Premier Laboratory University of Colorado MCDB, Room A3B40 Boulder, Colorado 80309 -----Original Message----- From: [email protected] [mailto:[email protected]] On Behalf Of Helen Ilsley Sent: Monday, July 17, 2006 3:15 AM To: [email protected] Subject: [Histonet] fibroblast marker Hi I wonder if anyone can help me. I am looking for a fibroblast marker which can cross react with any of the following: ...
Collagen type I production decreases with aging, leading to wrinkles and impaired skin function. Prostaglandin E2 (PGE2), a lipid-derived signaling molecule produced from arachidonic acid by cyclo-oxygenase, inhibits collagen production and induces matrix metallopeptidase 1 (MMP1) expression by fibroblasts in vitro. PGE2-induced collagen expression inhibition and MMP1 promotion are aging mechanisms. This study investigated the role of E-prostanoid 1 (EP1) in PGE2 signaling in normal human dermal fibroblasts (NHDFs). When EP1 expression was inhibited by EP1 small interfering RNA (siRNA), there were no significant changes in messenger RNA (mRNA) levels of collagen, type I, alpha 1 (COL1A1)/MMP1 between siRNA-transfected NHDFs and siRNA-transfected NHDFs with PGE2. This result showed that EP1 is a PGE2 receptor. Extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation after PGE2 treatment significantly increased by ~2.5 times. In addition, PGE2 treatment increased the intracellular Ca2+
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrotic lung disease for which there is no cure. Current therapeutics are only able to slow disease progression, therefore there is a need to explore alternative, novel treatment options. There is increasing evidence that the 3′, 5′ cyclic adenosine monophosphate (cAMP) pathway is an important modulator in the development of fibrosis, with increasing levels of cAMP able to inhibit cellular processes associated with IPF. In this study we investigate the expression of Gs-coupled G protein-coupled receptors (GPCR) on human lung fibroblasts (HLF), and explore which can increase cAMP levels, and are most efficacious at inhibiting proliferation and differentiation. Using TaqMan arrays we determined that fibroblasts express a range of Gs-coupled GPCR. The function of selected agonists at expressed receptors was then tested in a cAMP assay, and for their ability to inhibit fibroblast proliferation and differentiation. Expression analysis of
The importance of the tumor microenvironment on cancer growth and invasion are well appreciated (1-3), and the stiffness of the tumor stroma has been shown to drive tumorigenesis and invasion (8-10). However, in addition to matrix stiffness, interstitial flow is an important mechanical stress in the tumor stroma (5). By examining the interplay between tumor cells, fibroblasts, and interstitial flow, we showed that flow guides fibroblast invasion, leading to concurrent invasion of MDA-MB-435S tumor cells through the ECM. Without interstitial flow, fibroblasts did not affect tumor cell invasion.. TGF-β1 regulates a variety of tumor suppressive and promoting effects, including epithelial homeostasis, epithelial-to-mesenchymal transition, myofibroblast differentiation, and metastasis (36). TGF-β1 was necessary for interstitial flow-enhanced fibroblast invasion (Fig. 2A) but only indirectly involved in tumor cell invasion (Fig. 2D). We hypothesize that TGF-β1 may increase fibroblast invasion ...
TY - JOUR. T1 - c-Src enhances the spreading of src-/-fibroblasts on fibronectin by a kinase-independent mechanism. AU - Kaplan, Kenneth B.. AU - Swedlow, Jason R.. AU - Morgan, David O.. AU - Varmus, Harold E.. PY - 1995/6/15. Y1 - 1995/6/15. N2 - We have explored the role of the tyrosine kinase c-Src in cellular adhesion. Fibroblasts derived from src-/-mice (src-/-fibroblasts) exhibit a reduced rate of spreading on fibronectin. This defect is rescued by expression of wild-type chicken c-Src. Analyses of mutants suggest that c-Src increases the rate of cell spreading in src-/- fibroblasts through a kinase-independent mechanism requiring both the SH3 and SH2 domains. To further address the role of c-Src in adhesion, we examined the activity and subcellular distribution of c-Src during the adhesion of fibroblasts on fibronectin. We observed a transient increase in the specific kinase activity of c-Src accompanied by the partial dephosphorylation of the negative regulatory site Y527. Activation of ...
Identification of fibroblast derived factors in tumor progression has the potential to provide novel molecular targets for modulating tumor cell growth and metastasis. Multiple matrix metalloproteases (MMPs) are expressed by both mesenchymal and epithelial cells within head and neck squamous cell carcinomas (HNSCCs), but the relative importance of these enzymes and the cell source is the subject of controversy. The invasive potential of HNSCC tumor cells were assessed in vitro atop type I collagen gels in coculture with wild-type (WT), MMP-2 null, MMP-9 null or MT1-MMP null fibroblasts. A floor of mouth mouse model of HNSCC was used to assess in vivo growth after co-injection of FaDu tumor cells with MMP null fibroblasts. Here we report changes in tumor phenotype when FaDu HNSCCs cells are cocultured with WT, MMP-2 null, MMP-9 null or MT1-MMP null fibroblasts in vitro and in vivo. WT, MMP-2 null and MMP-9 null fibroblasts, but not MT1-MMP null fibroblasts, spontaneously invaded into type I collagen gels
Identification of fibroblast derived factors in tumor progression has the potential to provide novel molecular targets for modulating tumor cell growth and metastasis. Multiple matrix metalloproteases (MMPs) are expressed by both mesenchymal and epithelial cells within head and neck squamous cell carcinomas (HNSCCs), but the relative importance of these enzymes and the cell source is the subject of controversy. The invasive potential of HNSCC tumor cells were assessed in vitro atop type I collagen gels in coculture with wild-type (WT), MMP-2 null, MMP-9 null or MT1-MMP null fibroblasts. A floor of mouth mouse model of HNSCC was used to assess in vivo growth after co-injection of FaDu tumor cells with MMP null fibroblasts. Here we report changes in tumor phenotype when FaDu HNSCCs cells are cocultured with WT, MMP-2 null, MMP-9 null or MT1-MMP null fibroblasts in vitro and in vivo. WT, MMP-2 null and MMP-9 null fibroblasts, but not MT1-MMP null fibroblasts, spontaneously invaded into type I collagen gels
Fibroblast apoptosis is a critical component of normal repair and the acquisition of an apoptosis-resistant phenotype contributes to the pathogenesis of fibrotic repair. Fibroblasts from fibrotic lungs of humans and mice demonstrate resistance to apoptosis induced by Fas-ligand and prior studies have shown that susceptibility to apoptosis is enhanced when Fas (CD95) expression is increased in these cells. Moreover, prior work shows that Fas expression in fibrotic lung fibroblasts is reduced by epigenetic silencing of the Fas promoter. However, the mechanisms by which microenvironmental stimuli such as TGF-β1 and substrate stiffness affect fibroblast Fas expression are not well understood. Primary normal human lung fibroblasts (IMR-90) were cultured on tissue culture plastic or on polyacrylamide hydrogels with Youngs moduli to recapitulate the compliance of normal (400 Pa) or fibrotic (6400 Pa) lung tissue and treated with or without TGF-β1 (10 ng/mL) in the presence or absence of protein kinase
Wound healing is a complex process that requires an interplay between several cell types. Classically, fibroblasts have been viewed as producers of extracellular matrix, but more recently they have been recognized as orchestrators of the healing response, promoting and directing, inflammation and neovascularization processes. Compared to those from healthy tissue, inflammation-associated fibroblasts display a dramatically altered phenotype and have been described as sentinel cells, able to switch to an immunoregulatory profile on cue. However, the activation mechanism still remains largely uncharacterized. Nemosis is a model for stromal fibroblast activation. When normal human primary fibroblasts are deprived of growth support they cluster, forming multicellular spheroids. Clustering results in upregulation of proinflammatory markers such as cyclooxygenase-2 and secretion of prostaglandins, proteinases, cytokines, and growth factors. Fibroblasts in nemosis induce wound healing and tumorigenic ...
Cardiac fibrosis is a major component of heart disease and is a hallmark of decreased cardiac function. Currently, there are no treatments that attenuate fibrosis directly. This major hurdle can be overcome by targeting the resident fibroblast. Preliminary data demonstrates that loss of PDGFRα expression in the adult cardiac fibroblast lineage results in loss of over half of resident fibroblasts. A time course experiment revealed that in as little as 4 days after PDGFRα gene deletion fibroblast loss can observed. Based on the basal level of fibroblast proliferation (0.8%+/-0.9, i.e. 4 of 398 cells), we hypothesize that PDGFRα signaling is essential for fibroblast maintenance and that fibroblasts undergo rapid turnover. We have begun to elucidate which downstream signals of PDGFRα are involved the different roles of the fibroblast. Using a PDGFRα-dependent-PI3K-deficient mouse model, preliminary data indicates that PDGFRα-dependent PI3K signaling is involved in this cell survival response. ...
Cancer-associated fibroblasts (CAF) have been reported to support tumor progression by a variety of mechanisms. However, their role in the progression of non-small cell lung cancer (NSCLC) remains poorly defined. In addition, the extent to which specific proteins secreted by CAFs contribute directly to tumor growth is unclear. To study the role of CAFs in NSCLCs, a cross-species functional characterization of mouse and human lung CAFs was conducted. CAFs supported the growth of lung cancer cells in vivo by secretion of soluble factors that directly stimulate the growth of tumor cells. Gene expression analysis comparing normal mouse lung fibroblasts and mouse lung CAFs identified multiple genes that correlate with the CAF phenotype. A gene signature of secreted genes upregulated in CAFs was an independent marker of poor survival in patients with NSCLC. This secreted gene signature was upregulated in normal lung fibroblasts after long-term exposure to tumor cells, showing that lung fibroblasts are ...
Chronic kidney disease (CKD) is a global socioeconomic problem. It is characterised by the presence of differentiated myofibroblasts that, in response to TGF B-1, produce tissue fibrosis, leading to renal failure. Here we define a novel interaction between the SET9 lysine methyltransferase and SMAD3, the principle mediator of TGF B-1 signalling in myofibroblasts. We show that SET9 deficient fibroblasts exhibit globally altered gene expression profiles in response to TGF B-1, whilst overexpression of SET9 enhances SMAD3 transcriptional activity. We also show that SET9 facilitates SMAD3 nuclear import and controls SMAD3 protein degradation, in a manner involving ubiquitination. On a cellular level, we demonstrate that SET9 is broadly required for TGF B-1 effects in diseased primary renal fibroblasts; SET9 promotes fibroblast migration into wounds, expression of extracellular matrix proteins, collagen contractility and myofibroblast differentiation. Finally, we demonstrate that SET9 is recruited to ...
We performed subtractive and differential hybridization for transcript comparison between murine fibroblasts and isogenic epithelium, and observed only a few novel intracellular genes which were relatively specific for fibroblasts. One such gene encodes a filament-associated, calcium-binding protein, fibroblast-specific protein 1 (FSP1). The promoter/enhancer region driving this gene is active in fibroblasts but not in epithelium, mesangial cells or embryonic endoderm. During development, FSP1 is first detected by in situ hybridization after day 8.5 as a postgastrulation event, and is associated with cells of mesenchymal origin or of fibroblastic phenotype. Polyclonal antiserum raised to recombinant FSP1 protein stained the cytoplasm of fibroblasts, but not epithelium. Only occasional cells stain with specific anti-FSP1 antibodies in normal parenchymal tissue. However, in kidneys fibrosing from persistent inflammation, many fibroblasts could be identified in interstitial sites of collagen ...
Human Pulmonary Fibroblast MicroRNA ...
Resident fibroblasts synthesize the cardiac extracellular matrix, and can undergo phenotype conversion to myofibroblasts to augment matrix production, impairing function and contributing to organ failure. A significant gap in our understanding of the transcriptional regulation of these processes exists. Given the key role of this phenotype conversion in fibrotic disease, the identification of such novel transcriptional regulators may yield new targets for therapies for fibrosis. Using explanted primary cardiac fibroblasts in gain- and loss-of-function studies, we found that scleraxis critically controls cardiac fibroblast/myofibroblast phenotype by direct transcriptional regulation of myriad genes that effectively define these cells, including extracellular matrix components and α-smooth muscle actin. Scleraxis furthermore potentiated the TGFβ/Smad3 signaling pathway, a key regulator of myofibroblast conversion, by facilitating transcription complex formation. While scleraxis promoted fibroblast to
Survivin encoded by BIRC5 belongs to the group of proteins that inhibit apoptosis. It consists of the BIR and α-helical C domains. In addition to its inhibitory activity, it plays an important role in cell cycle regulation. Adalimumab is an immunosuppressive drug, a recombinant human anti-TNF-α monoclonal antibody. It is used in the treatment of autoimmune diseases.The aim of the study was to evaluate changes in the expression of BIRC5 and genes encoding apoptosis inhibitors (IAP), depending on the exposure time of the cells to adalimumab. The study material consisted of normal human dermal fibroblasts (NHDF) cultured under standard conditions in the presence of adalimumab (8µg/mL) for 2, 8 and 24 hours. The expression profile of genes associated with apoptosis was determined with the use of HG-U133A 2.0 oligonucleotide microarrays (Affymetrix). The comparative analysis was performed with one-way ANOVA and Tukey's HSD tests (p,0.05) using the PL-Grid Infrastructure ...
The effect of serum deprivation on proliferating cells is well known, in contrast its role on primary cell cultures, at confluence, has not been deeply investigated. Therefore, in order to explore the response of quiescent cells to serum deprivation, ubiquitous mesenchymal cells, as normal human dermal fibroblasts, were grown, for 48 h after confluence, in the presence or absence of 10% FBS. Fibroblast behaviour (i.e. cell morphology, cell viability, ROS production and elastin synthesis) was evaluated morphologically and biochemically. Moreover, the protein profile was investigated by 2-DE and differentially expressed proteins were identified by MS. Serum withdrawal caused cell shrinkage but did not significantly modify the total cell number. ROS production, as evaluated by the dihydroethidium (DH2) probe, was increased after serum deprivation, whereas elastin synthesis, measured by a colorimetric method, was markedly reduced in the absence of serum. By proteome analysis, 41 proteins appeared to ...
Results We observed increased expression of JMJD3 in SSc skin compared to healthy controls. Fibroblast-specific overexpression of JMJD3 was also reflected in experimental fibrosis models. TGFβ upregulated JMJD3. Inhibition of JMJD3 increased H3K27me3 in vitro and in vivo. Inhibition of JMJD3 reverted the activated fibroblast phenotype in SSc fibroblasts and decreased the expression of contractile fibers and of α-smooth muscle actin. In addition, JMJD3 inhibition reduced the basal and TGFβ induced collagen secretion of SSc fibroblasts. JMJD3 regulated the TGFβ induced expression of Fra2. GSKJ4 reverted the TGFβ induced reduction of H3K27me3 at the Fra2 promotor. Moreover, the anti-fibrotic effects of JMJD3 inhibition were evened in Fra2 knockout fibroblasts. Overexpression of Fra2 in JMJD3-knockdown fibroblasts restored the profibrotic effect of JMJD3. In vivo, inhibition of JMJD3 ameliorated fibrosis in bleomycin- and TopoI- induced experimental fibrosis and reduced dermal thickening, ...
Cancer-associated fibroblasts (CAF) remain a poorly characterized, heterogeneous cell population. Here we characterized two previously described tumor-promoting CAF sub-types, smooth muscle actin (SMA)-positive myofibroblasts and senescent fibroblasts, identifying a novel link between the two. Analysis of CAF cultured ex vivo, showed that senescent CAF are predominantly SMA-positive; this was confirmed by immunochemistry in head & neck (HNSCC) and esophageal (EAC) cancers. In vitro, we found that fibroblasts induced to senesce develop molecular, ultrastructural and contractile features typical of myofibroblasts and this is dependent on canonical TGF-β signaling. Similar to TGF-β1-generated myofibroblasts, these cells secrete soluble factors that promote tumor cell motility. However, RNA-sequencing revealed significant transcriptomic differences between the two SMA-positive CAF groups, particularly in genes associated with extracellular matrix (ECM) deposition and organization, which
Both in vivo and in vitro studies have demonstrated that fibroblasts contribute to tumor formation and growth rates (6) , and can be thought of as contracted farmers used by tumors to prepare the microenvironment. Fibroblasts coinoculated with breast or bladder tumor cell lines in nude mice shorten tumor latency and increase tumor growth (7) . Fibroblasts cultured from malignant tumors have stimulatory effects on MCF-7 cells, whereas fibroblasts cultured from normal tissue are inhibitory (8) . Phenotypic differences among tumor-associated fibroblasts have also been seen. Fibroblasts with smooth muscle differentiation, termed myofibroblasts, are abundant in the stromal cells of malignant breast tissue but are rarely seen in normal breast tissue (9) . These findings suggest that tumor-associated fibroblasts are functionally distinct compared with fibroblasts that are not in the tumor microenvironment, and subpopulations of fibroblast may perform specialized functions to coordinate events ...
Idiopathic pulmonary fibrosis (IPF) is a progressive, severely debilitating disease with a high mortality rate. Nintedanib (BIBF 1120) is a receptor tyrosine kinase inhibitor specific for platelet-derived growth factor receptor, fibroblast growth factor receptor and vascular endothelial growth factor receptor. Its effect on IPF disease progression measured by lung function decline has been investigated in two replicate Phase III clinical trials (INPULSIS-1 and -2) in patients with IPF. Interleukin-1 beta (IL-1β) is a potent pro-fibrotic mediator stimulating fibroblast proliferation a hallmark of IPF.. Aim: To determine the effect of nintedanib on proliferation rate of IL-1β-stimulated primary human lung fibroblasts.. Methods: Primary human lung fibroblasts from patients with IPF (IPF-HPF) and from non-fibrotic control donors (HPF) were incubated with nintedanib (1 nM - 1000 nM) for 30 min. Subsequently the cells were stimulated with IL-1β and cell proliferation was assessed by BrdU assay ...
3T3 cells come from a cell line established in 1962 by two scientists then at the Department of Pathology in the New York University School of Medicine, George Todaro and Howard Green. The 3T3 cell line has become the standard fibroblast cell line. Todaro and Green originally obtained their 3T3 cells from Swiss albino mouse embryo tissue. The 3T3 designation refers to the abbreviation of 3-day transfer, inoculum 7005300000000000000♠3×105 cells. This cell line was originally established from the primary mouse embryonic fibroblast cells that were cultured by the designated protocol, so-called 3T3 protocol. The primary mouse embryonic fibroblast cells were transferred (the T) every 3 days (the first 3), and inoculated at the rigid density of 7005300000000000000♠3×105 cells per 20 cm2 dish (the second 3) continuously. The spontaneously immortalized cells with stable growth rate were established after 20 to 30 generations in culture, and then named 3T3 cells. Specifically, ...
TY - JOUR. T1 - Foetal-to-adult transitions in fibroblast phenotype. T2 - their possible relevance to the pathogenesis of cancer. AU - Schor, S L. AU - Schor, A M. PY - 1987. Y1 - 1987. N2 - We have previously shown that the migration of foetal, adult and transformed fibroblasts into three-dimensional collagen gels is differentially affected by plating cell density. We now present data indicating that the migration of these fibroblasts is also differentially affected by local cell density in microdomains of the gel surface. In this article we discuss the possible biochemical and behavioural mechanisms that may contribute to the different migratory phenotypes expressed by foetal, adult and transformed fibroblasts; these include: (1) cell-induced alterations in the orientation and or packing density of collagen fibres in the gel; (2) deposition of specific matrix macromolecules by the fibroblasts; (3) social interactions between the cells; and (4) secretion of soluble factors affecting cell ...
Fibroblasts are a main player in the tumor-inhibitory microenvironment. Upon tumor initiation and progression, fibroblasts can lose their tumor-inhibitory capacity and promote tumor growth. The molecular mechanisms that underlie this switch have not been defined completely. Previously, we identified four proteins overexpressed in cancer-associated fibroblasts and linked to Rho GTPase ... read more signaling. Here, we show that knocking out the Ras homolog family member A (RhoA) gene in normal fibroblasts decreased their tumor-inhibitory capacity, as judged by neighbor suppression in vitro and accompanied by promotion of tumor growth in vivo. This also induced PC3 cancer cell motility and increased colony size in 2D cultures. RhoA knockout in fibroblasts induced vimentin intermediate filament reorganization, accompanied by reduced contractile force and increased stiffness of cells. There was also loss of wide F-actin stress fibers and large focal adhesions. In addition, we observed a significant ...
Background: Cardiac fibrosis is associated with a variety of heart diseases including atrial fibrillation (AF). Cardiac fibroblast is the major cell type in cardiac fibrogenesis cascade. However, the biological as well as electrophysiological properties of cardiac fibroblasts are not fully understood. In this study, we investigated the functional expression of voltage-gated and non-voltage-gated ion channels in artial fibroblasts from AF patients and SR patients, and their contribution to atrial fibrogenesis.. Methods: With informed consent, right atrial biopsies were obtained from AF patients or sinus rhythm (SR) patients undergoing cardiac surgery. Fibroblasts were dissociated from the biopsy samples from SR patients or AF patients. The freshly isolated cells were used for patch-clamp and ratio Ca2+-imaging experiments.. Results: We found that there are two types of voltage-gated outward potassium channels in the fibroblasts from SR patients: one is transient outward potassium current (Ito), ...
Cell lines. EBV-transformed LCLs and primary dermal fibroblasts were established as previously described (57). Previously used LCLs from an unaffected individual, AG1010 (24), termed control LCLs, were used in all experiments. In experiments with primary dermal fibroblasts, a previously used cell line from a healthy individual, 82-6 (30), termed control fibroblasts 1, was used for all experiments. To corroborate the findings in some experiments, additional cell lines from unaffected individuals (IMR-90, NHDF, and 1101-SK) were used and are termed control fibroblasts 2, 3, and 4, respectively. 88-1 normal fibroblasts were also used. Primary dermal fibroblasts were maintained in DMEM supplemented with 10% FBS. Human osteosarcoma (U2OS) and non-small-cell lung cancer (H1299) cell lines were also maintained in DMEM supplemented with 10% FBS. LCLs were maintained in RPMI medium supplemented with 10% FBS. Cell lines were obtained from Junko Oshima, Lyubomir Vassilev (Serono Research and Development ...
COPD is associated with disturbed tissue repair, possibly due to TGF-β-regulated miRNA changes in fibroblasts. Our aim was to identify TGF-β-regulated miRNAs and their differential regulation and expression in COPD compared to control fibroblasts. Small RNA sequencing was performed on TGF-β-stimulated and unstimulated lung fibroblasts from 15 COPD patients and 15 controls. Linear regression was used to identify TGF-β-regulated and COPD-associated miRNAs. Interaction analysis was performed to compare miRNAs that responded differently to TGF-β in COPD and control. Re-analysis of previously generated Ago2-IP data and Enrichr were used to identify presence and function of potential target genes in the miRNA-targetome of lung fibroblasts. In total, 46 TGF-β-regulated miRNAs were identified in COPD and 86 in control fibroblasts (FDR , 0.05). MiR-27a-5p was the most significantly upregulated miRNA. MiR-148b-3p, miR-589-5p and miR-376b-3p responded differently to TGF-β in COPD compared to control ...
AppliedStemCell eCommerce Platform Human Skin Cells (Dermal Fibroblasts) (DMD) [ASE-5014] - Catalog Number ASE-5014 Quantity 5.0 x 105 cells/mL Product Information Description Human fibroblasts are derived from cultured skin explants. These fibroblasts ar
AppliedStemCell eCommerce Platform Human Skin Cells (Dermal Fibroblasts) (LCP) [ASE-5055] - Catalog Number ASE-5055 Quantity 5.0 x 105 cells/mL Product Information Description Human fibroblasts are derived from cultured skin explants. These fibroblasts ar
Fibrotic diseases are characterized by the accumulation of extracellular matrix together with distortion and disruption of tissue architecture. Phosphodiesterase (PDE)4 inhibitors, by preventing the breakdown of cAMP, can inhibit fibroblast functions and may be able to mitigate tissue remodeling. Transforming growth factor (TGF)-β1, a mediator of fibrosis, can potentially modulate cAMP by altering PGE2 metabolism. The present study assessed whether PDE4 inhibitors functionally antagonize the profibrotic activity of fibroblasts stimulated by TGF-β1. The PDE4 inhibitors roflumilast and rolipram both inhibited fibroblast-mediated contraction of three-dimensional collagen gels and fibroblast chemotaxis toward fibronectin in the widely studied human fetal lung fibroblast strain HFL-1 and several strains of fibroblasts from adult human lung. Roflumilast was ~10-fold more potent than rolipram. There was a trend for PDE4 inhibitors to inhibit more in the presence of TGF-β1 (0.05 , P , 0.08). The ...
TY - JOUR. T1 - In Crohns disease fibrosis-reduced expression of the miR-29 family enhances collagen expression in intestinal fibroblasts.. AU - Nijhuis, Anke. AU - Biancheri, Paolo. AU - Lewis, Amy. AU - Bishop, Cleo L.. AU - Giuffrida, Paolo. AU - Chan, Christopher. AU - Feakins, Roger. AU - Poulsom, Richard. AU - Di Sabatino, Antonio. AU - Corazza, Gino Roberto. AU - MacDonald, Thomas T.. AU - Lindsay, James O.. AU - Silver, Andrew R.. PY - 2014. Y1 - 2014. N2 - Intestinal fibrosis with stricture formation is a complication of CD (Crohns disease) that may mandate surgical resection. Accurate biomarkers that reflect the relative contribution of fibrosis to an individual stricture are an unmet need in managing patients with CD. The miRNA-29 (miR-29) family has been implicated in cardiac, hepatic and pulmonary fibrosis. In the present study, we investigated the expression of miR-29a, miR-29b and miR-29c in mucosa overlying a stricture in CD patients (SCD) paired with mucosa from non-strictured ...
During the last decade it has become clear that periodontal ligament fibroblasts may contribute to the in vitro differentiation of osteoclasts. We surveyed the current findings regarding their osteoclastogenesis potential. Periodontal ligament fibroblasts have the capacity to select and attract osteoclast precursors and subsequently to retract and enable migration of osteoclast precursors to the bone surface. There, fusion of precursors takes place, giving rise to osteoclasts. The RANKL-RANK-osteoprotegerin (OPG) axis is considered crucial in this process. Periodontal ligament fibroblasts produce primarily OPG, an osteoclastogenesis-inhibitory molecule. However, they may be influenced in vivo by direct or indirect interactions with bacteria or by mechanical loading. Incubation of periodontal ligament fibroblasts with bacteria or bacterial components causes an increased expression of RANKL and other osteoclastogenesis-stimulating molecules, such as tumor necrosis factor-α and macrophage-colony ...
TY - JOUR. T1 - The effect of carboxymethyl-chitosan on proliferation and collagen secretion of normal and keloid skin fibroblasts. AU - Chen, Xi Guang. AU - Wang, Zhen. AU - Liu, Wan Shun. AU - Park, Hyun Jin. PY - 2002/12. Y1 - 2002/12. N2 - In this study, different molecular weight CM-chitosans were prepared and the effects on the growth and collagen secretion of normal skin fibroblasts and keloid fibroblasts were investigated in vitro. CM-chitosan promoted the proliferation of the normal skin fibroblast significantly but inhibited the proliferation of keloid fibroblast. The higher CM-chitosan concentration had a higher initial effect and the lower CM-chitosan concentration had a longer affecting time to the normal skin fibroblast. The lower molecular weight CM-chitosan had significant twofold activities. The CM-chitosan could reduce the ratio of type I/III collagen in keloid fibroblast by inhibiting the secretion of collagen type I; and had no effect on the secretion of types I and III ...
Normal human fibroblasts display a limited lifespan in culture, which is due to a steadily decreasing fraction of cells that are able to proliferate. Using antibodies that react with antigens present in proliferating cells only, in an indirect immunofluorescence assay, we have estimated the fraction of proliferating cells in cultures of normal human fibroblasts. Furthermore, we have estimated the rate of decline in the fraction of proliferating cells during the process of cellular ageing by application of the assay to normal human fibroblasts throughout their lifespan in culture. Werners Syndrome is an autosomal recessive disease in which individuals display symptoms of ageing prematurely. Werners Syndrome fibroblasts display a reduced lifespan in culture compared with normal human fibroblasts. Like normal human fibroblasts, the growth of Werners Syndrome fibroblasts is characterised by a decreasing fraction of cells reacting with the proliferation-associated antibodies throughout their ...
Keloid pathogenesis occurs due to the longer duration of inflammation and the increase in the production of several factors such as TGF-β1 that causes the increase of fibroblast proliferation and collagen synthesis. The role of B4 Leukotriene (LTB4) in keloid pathogenesis particularly in the inflammation phase and tissue proliferation has not been clearly elucidated. The present study was to analyze the levels of LTB4, TGF-β1 and collagen in keloid fibroblast and normal skin fibroblast. Fibroblasts were cultured by applying explant method to the keloid and normal skin of the petient with the keloid. The measurement of the levels of LTB4, TGF-β1 and collagen was conducted by using Elisa method and triplicate was conducted subsequently. Statistic testing was performed through unpaired t test. The experiment was carried out in cell culture laboratory of The Faculty of Medicine Padjajaran University Bandung. The levels of LTB4, TGF-β1 are higher in keloid fibroblast, despite the fact that it does not
Proteoglycan from salmon nasal cartilage promotes in vitro wound healing of fibroblast monolayers via the CD44 receptorProteoglycan from salmon nasal cartilage promotes in vitro wound healing of fibroblast monolayers via the CD44 receptor ...
Enalaprilat (Ena.), an angiotensin II (Ang II) converting enzyme inhibitor (ACEI), can produce some therapeutic effects on hypertension, ventricular hypertrophy and myocardial remodeling in clinic, but its precise mechanism, especially its signaling pathways remain elusive. In this study, cardiac fibroblasts (CFb) was isolated by the trypsin digestion method; a BrdU proliferation assay was adopted to determine cell proliferation; an immunofluorescence assay was used to measure intracellular reactive oxygen species (ROS); immunocytochemistry staining and Western blotting assay were used to detect phosphorylated p38 mitogen activated protein kinase (p-p38MAPK) and transforming growth factor-β1 (TGF-β1) protein expression, respectively. The results showed that Ang II (10-7 M) stimulated the cardiac fibroblast proliferation which was inhibited by NAC (an antioxidant), SB203580 (a p38MAPK inhibitor) or enalaprilat; Ang II caused an burst of intracellular ROS level within thirty minutes, an increase in p
Over the last years, electronic cigarettes (ECs) have become more popular, particularly in individuals who want to give up smoking tobacco. The aim of the present study was to assess the influence of the different e-smoking liquids on the viability and proliferation of human periodontal ligament fibroblasts. For this study six test solutions with components from ECs were selected: lime-, hazelnut- and menthol-flavored liquids, nicotine, propylene glycol, and PBS as control group. The fibroblasts were incubated up to 96 h with the different liquids, and cell viability was measured by using the PrestoBlue® reagent, the ATP detection and the migration assay. Fluorescence staining was carried out to visualize cell growth and morphology. Data were statistically analyzed by two-tailed one-way ANOVA. The cell viability assay showed that the proliferation rates of the cells incubated with nicotine or the various flavored liquids of the e-cigarettes were reduced in comparison to the controls, though not all
OBJECTIVE To compare the mechanotransduction caused by cyclic and static mechanical strains in human periodontal ligament fibroblasts (hPDLFs) cultured under identical conditions. MATERIALS AND METHODS hPDLFs, originating from the same donors, were exposed either to cyclic or to static tensile strain using specially designed devices and under identical culture conditions. Activation of all members of mitogen-activated protein kinases (MAPKs) was monitored by western immunoblot analysis. Expression levels of immediate/early genes c-fos and c-jun were assessed with quantitative real-time polymerase chain reaction. RESULTS Time course experiments revealed that both types of stresses activate the three members of MAPK, that is ERK, p38, and JNK, with cyclic stress exhibiting a slightly more extended activation. Further downstream, both stresses upregulate the immediate/early genes c-fos and c-jun, encoding components of the activator protein-1 (AP-1), a key transcription factor in osteoblastic ...
TY - JOUR. T1 - Differential binding of 125I-IGF-I preparations to human fibroblast monolayers. AU - Conover, C. A.. AU - Misra, P.. AU - Hintz, R. L.. AU - Rosenfeld, R. G.. N1 - Copyright: Copyright 2020 Elsevier B.V., All rights reserved.. PY - 1988. Y1 - 1988. N2 - Specific, high affinity binding of 125I-IGF-I to the type I IGF receptor on human fibroblast monolayers was not altered by varying feeding schedules, serum lots, washing procedures, or incubation times and temperatures. However, markedly different competitive binding curves were obtained when different iodinated IGF-I preparations were used. Five of six radioligands bound preferentially to the type I IGF receptor on human fibroblast monolayers, with 50% displacement at 4-8 μg/l unlabelled IGF-I; with one radioligand a paradoxical 20-200% increase in 125I-IGF-I binding was observed at low concentrations of unlabelled IGF-I, while concentrations as high as 100 μg/l IGF-I failed to displace this radioligand. The latter binding ...
TY - JOUR. T1 - Lysocardiolipin acyltransferase regulates TGF-β mediated lung fibroblast differentiation. AU - Huang, Long Shuang. AU - Jiang, Peiyue. AU - Feghali-Bostwick, Carol. AU - Reddy, Sekhar P.. AU - Garcia, Joe G.N.. AU - Natarajan, Viswanathan. PY - 2017/11. Y1 - 2017/11. N2 - Lysocardiolipin acyltransferase (LYCAT), a cardiolipin remodeling enzyme, plays a key role in mitochondrial function and vascular development. We previously reported that reduced LYCAT mRNA levels in peripheral blood mononuclear cells correlated with poor pulmonary function outcomes and decreased survival in IPF patients. Further LYCAT overexpression reduced lung fibrosis, and LYCAT knockdown accentuated experimental pulmonary fibrosis. NADPH Oxidase 4 (NOX4) expression and oxidative stress are known to contribute to lung fibroblast differentiation and progression of fibrosis. In this study, we investigated the role of LYCAT in TGF-β mediated differentiation of human lung fibroblasts to myofibroblasts, and ...
TY - JOUR. T1 - Effects of (1→3), (1→6)-β-D-glucan behavior in human dermal fibroblast cells under serum starvation. AU - Woo, Yeon I.. AU - Son, Hyun Joo. AU - Lim, Hye Ryeon. AU - Lee, Mi Hee. AU - Baek, Hyun Sook. AU - Tsubaki, Kazufumi. AU - Park, Jong Chul. PY - 2007. Y1 - 2007. N2 - Glucans have been reported to stimulate immunity and to promote wound healing. Adult human dermal fibroblast (aHDF) cultured in serum free (serum-starvation). Proliferation of aHDF was measured at various concentrations of β-glucan by MTT assay, and migration was observed for 36h on microscope. The result of fibroblast bioassay, β-glucan had positive influence. In this study, the direct effects of β-glucan on proliferation and migration of human dermal fibroblasts were examined in vitro. That means β-D-glucan has the effect to enhance proliferation and aHDF migration speed, and has the potential as a wound healing agent.. AB - Glucans have been reported to stimulate immunity and to promote wound ...
The roles of MEK, ERK, the epsilon and alpha isoforms of protein kinase C (PKC), and caveolin-1 in regulating collagen expression were studied in normal lung fibroblasts. Knocking down caveolin-1 gave particularly striking results. A 70% decrease caused a 5-fold increase in MEK/ERK activation and collagen expression. The combined data reveal a branched signaling pathway. In its central portion MEK activates ERK, leading to increased collagen expression. Two branches converge on MEK/ERK. In one, increased PKCepsilon leads to MEK/ERK activation. In another, increased PKCalpha induces caveolin-1 expression, which in turn inhibits MEK/ERK activation and collagen expression. Lung fibroblasts from scleroderma patients with pulmonary fibrosis showed altered signaling. Consistent with their overexpression of collagen, scleroderma lung fibroblasts contain more activated MEK/ERK and less caveolin-1 than normal lung fibroblasts. Because cutaneous fibrosis is the hallmark of scleroderma, we also studied ...
Chronic kidney disease (CKD) is a leading cause of end stage renal disease (ESRD) and cardiovascular morbidity and mortality worldwide, resulting in a growing social and economic burden. The prevalence and burden of CKD is anticipated to further increase over the next decades as a result of aging. In the pathogenesis of CKD, irrespective of the etiology, resident fibroblasts are key players and have been demonstrated to play crucial roles for disease initiation and progression. In response to injury, resident fibroblasts transdifferentiate into myofibroblasts that express alpha smooth muscle actin (αSMA) and have an increased capacity to produce large amounts of extracellular matrix (ECM) proteins, leading to renal fibrosis. In addition to this fundamental role of fibroblasts as drivers for renal fibrosis, growing amounts of evidence have shown that resident fibroblasts are also actively involved in initiating and promoting inflammation during kidney injury. During the myofibroblastic transition
Nature Reviews Nephrology. fibroblast synovial cells and chondrocytes [13]. Obese osteoarthritis patients exhibit an inflammatory synovial fibroblast phenotype, which is regulated by the long non coding RNA MALAT1 November 2019 Arthritis and Rheumatology 72(4) Because we focused on the synovium, mTOR and lysophosphatidic acid were not described in greater detail, as these factors were only found to be elevated in chondrocytes/cartilage and not in synovial fibroblasts or the synovium. eCollection 2019. Bank RA Verzijl N Lafeber FP Tekoppele JM. In the past, OA was considered a disease of the cartilage only. The Smad-independent TAK-1 pathway has been shown to have profibrotic effects in regulating the expression of ECM proteins, including collagens and fibronectin [41]. OBJECTIVE: Changes in rheumatoid arthritis synovial fibroblast (RASF) gene expression are usually defined by a comparison to osteoarthritis synovial fibroblasts (OASFs). CTGF, like TGF-β, is found to be elevated in many fibrotic ...
Authors: Tang CH, Hsu CJ, Yang WH, Fong YC. Patients with rheumatoid arthritis (RA) are at increased risk of developing infections and appear to be particularly susceptible to septic arthritis. Lipoteichoic acid (LTA), a cell wall component of Gram-positive bacteria is an amphiphilic, negatively charged glycolipid. However, the effects of LTA on human synovial fibroblasts are largely unknown. We investigated the signaling pathway involved in IL-6 production stimulated by LTA in rheumatoid arthritis synovial fibroblasts (RASF). LTA caused concentration- and time-dependent increases in IL-6 production. LTA-mediated IL-6 production was attenuated by Toll-like receptor 2 (TLR2) monoclonal antibody or siRNA. Pretreatment with PKCdelta inhibitor (rottlerin), c-Src inhibitor (PP2), AP-1 inhibitor (tanshinone IIA) and NF-kappaB inhibitor (PDTC and TPCK) also inhibited the potentiating action of LTA. However, focal adhesion kinase (FAK) mutant and siRNA did not affect LTA-mediated IL-6 production. ...
TY - JOUR. T1 - Modulation of fibroblast morphology and adhesion during collagen matrix remodeling. AU - Tamariz, Elisa. AU - Grinnell, Frederick. N1 - Copyright: Copyright 2005 Elsevier B.V., All rights reserved.. PY - 2002/11/1. Y1 - 2002/11/1. N2 - When fibroblasts are placed within a three-dimensional collagen matrix, cell locomotion results in translocation of the flexible collagen fibrils of the matrix, a remodeling process that has been implicated in matrix morphogenesis during development and wound repair. In the current experiments, we studied formation and maturation of cell-matrix interactions under conditions in which we could distinguish local from global matrix remodeling. Local remodeling was measured by the movement of collagen-embedded beads towards the cells. Global remodeling was measured by matrix contraction. Our observations show that no direct relationship occurs between protrusion and retraction of cell extensions and collagen matrix remodeling. As fibroblasts globally ...
TY - JOUR. T1 - WISP1, a pro-mitogenic, pro-survival factor, mediates tumor necrosis factor-α (TNF-α)-stimulated cardiac fibroblast proliferation but inhibits TNF-α-induced cardiomyocyte death. AU - Venkatachalam, Kaliyamurthi. AU - Venkatesan, Balachander. AU - Valente, Anthony J.. AU - Melby, Peter. AU - Nandish, Sailesh. AU - Reusch, Jane E B. AU - Clark, Robert A.. AU - Chandrasekar, Bysani. PY - 2009/5/22. Y1 - 2009/5/22. N2 - WNT1-inducible signaling pathway protein-1 (WISP1), a member of the CYR61/CTGF/Nov family of growth factors, can mediate cell growth, transformation, and survival. Previously we demonstrated that WISP1 is up-regulated in post-infarct heart, stimulates cardiac fibroblast proliferation, and is induced by the proinflammatory cytokine tumor necrosis factor-α (TNF-α). Here we investigated (i) the localization of TNF-α and WISP1 in post-infarct heart, (ii) the mechanism of TNF-α-mediated WISP1 induction in primary human cardiac fibroblasts (CF), (iii) the role of ...
Leukoregulin (LR), a T-cell-derived growth factor, modulates fibroblast functions in vitro [Mauviel, Rédini, Hartmann, Loyau & Pujol (1991) J. Cell Biol. 113, 1455-1462]. In the present study, incubation of human dermal fibroblasts with LR (0.1-2 units/ml) resulted in decreases in the mRNA steady-state levels for alpha 1(I), alpha 2(I) and alpha 1(III), but not alpha 2(V), collagen genes. LR also down-regulated alpha 2(I) collagen promoter activity in transient cell transfections of control cells as well as those incubated with transforming growth factor-beta, a potent up-regulator of collagen type I gene expression. Thus LR is a strong inhibitor of type I collagen gene expression, acting at the level of transcription. ...
Huang, S.-M., Zuo, X., Li, J. J., Li, S. F. Y., Bay, B. H. and Ong, C. N. (2012), Metabolomics Studies Show Dose-Dependent Toxicity Induced by SiO2 Nanoparticles in MRC-5 Human Fetal Lung Fibroblasts. Advanced Healthcare Materials, 1: 779-784. doi: 10.1002/adhm.201200114 ...
Cynomolgus Monkey Primary Cardiac Fibroblasts. Catalog No. MK-6049. Suggested Medium: Catalog No. M2267 Fibroblast Medium /w Kit (500 ml). Product Description. Monkey Primary Cardiac Fibroblasts from Cell Biologics are isolated from tissue of Cynomolgus Monkey. Monkey Primary Cardiac Fibroblasts are grown in T25 tissue culture flasks pre-coated with gelatin-based solution for 0.5 hour and incubated in Cell Biologics Culture Complete Growth Medium generally for 3-7 days. Cultures are then expanded. Prior to shipping, cells are detached from flasks and immediately cryo-preserved in vials. Each vial contains at least 1x106 cells per ml and is delivered frozen. Monkey Primary Cardiac Fibroblasts are negative for bacteria, yeast, fungi, and mycoplasma. Cells can be expanded for 3-6 passages at a split ratio of 1:3 under the cell culture conditions specified by Cell Biologics. Repeated freezing and thawing of cells is not recommended.. Laboratory Applications. Standard biochemical procedures performed ...
TY - JOUR. T1 - Clinical variation in X-linked adrenoleukodystrophy. T2 - Fatty acid and lipid metabolism in cultured fibroblasts. AU - Boles, Debra J.. AU - Craft, Debra A.. AU - Padgett, David A.. AU - Loria, Roger M.. AU - Rizzo, William B.. PY - 1991/2. Y1 - 1991/2. N2 - To determine whether the clinical phenotype of ALD correlates with the extent of metabolic abnormality, we investigated VLFA metabolism in cultured fibroblasts from patients with the clinically severe childhood form of ALD and the milder AMN variant. No differences were seen in the content of neutral lipids or phospholipids, in incorporation of [1-14C]lignocerate into cellular lipids, or in the fatty acid composition of fibroblasts from patients with childhood ALD or AMN. [1-14C]Lignocerate oxidation was deficient to a similar extent (35-40% of normal) in both intact fibroblasts and cell homogenates from patients with childhood ALD and AMN. With the use of fibroblast homogenates, oxidation of lignocerate was partially ...
Chronic airway diseases like COPD and asthma are usually accompanied with airway fibrosis. Myofibroblasts, which are characterized by expression of smooth muscle actin (alpha-SMA), play an important role in a variety of developmental and pathological processes, including fibrosis and wound healing. Sphingosylphosphorylcholine (SPC), a sphingolipid metabolite, has been implicated in many physiological and pathological conditions. The current study tested the hypothesis that SPC may modulate tissue remodeling by affecting the expression of a-SMA in human fetal lung fibroblast (HFL-1) and fibroblast mediated gel contraction. The results show that SPC stimulates a-SMA expression in HFL-1 and augments HFL-1 mediated collagen gel contraction in a time- and concentration-dependent manner. The a-SMA protein expression and fibroblast gel contraction induced by SPC was not blocked by TGF-beta 1 neutralizing antibody: However, it was significantly blocked by S1P2 receptor antagonist JTE-013, the ...
Several cell surface proteins (Mr=120,000, 90,000, 63,000 and 47,000) apparently integral to embryonic fibroblast plasma membranes were extracted with detergent and isolated by collagen affinity chromatography. Certain of these proteins (Mr=120,000, 90,000 and 47,000) were specifically eluted from collagen affinity columns by synthetic peptides containing the amino acid sequence arginyl-glycyl-aspartic acid (RGD). These data show that a number of collagen binding proteins exist on the embryonic fibroblast cell surface. Some of the proteins may be collagen receptors binding to RGD sequences in the collagen molecule while at least one of the proteins (Mr=63,000) recognizes features other than RGD. ...
Synovial fibroblasts isolated from human synovium. High quality synovial fibroblasts from human synovium cryopreserved and provided as frozen aliquots. Human synovial fibroblasts can be from patients with osteoarthritis, rheumatoid arthritis, or with no
Synovial fibroblasts isolated from human synovium. High quality synovial fibroblasts from human synovium cryopreserved and provided as frozen aliquots. Human synovial fibroblasts can be from patients with osteoarthritis, rheumatoid arthritis, or with no
TY - CONF. T1 - Effects of THz radiation on human fibroblasts in-vitro: Exposure set-up and biological endpoints. AU - Gallerano, G.P.. AU - Giovenale, E.. AU - Nenzi, P.. AU - De Amicis, A.. AU - De Sanctis, S.. AU - Di Cristofaro, S.. AU - Franchini, V.. AU - Lista, F.. AU - Regalbuto, E.. AU - Sgura, A.. AU - Coluzzi, E.. AU - Bei, R.. AU - Fantini, M.. AU - Benvenuto, M.. AU - Masuelli, L.. PY - 2014/11/13. Y1 - 2014/11/13. N2 - In vitro exposures of human fibroblasts have been performed in a wide band between 100 and 150 GHz using the ENEA Compact Free Electron Laser. The methodology of the study and the exposure set-up will be presented together with an analysis of preliminary results.. AB - In vitro exposures of human fibroblasts have been performed in a wide band between 100 and 150 GHz using the ENEA Compact Free Electron Laser. The methodology of the study and the exposure set-up will be presented together with an analysis of preliminary results.. UR - ...
Senussi O.A.; Carwright T.; Thompson P., 1979: Resolution of human fibroblast interferon into 2 distinct classes by thiol exchange chromatography
The understanding of cell-surface interactions plays an important role for the biomaterials development and bioengineering. Although it is already known that amine groups increase the cell adhesion and proliferation, the influence of amine layers properties on cell viability is the subject of further investigation. In this work, amine-rich coatings were prepared by low pressure plasma polymerization of cyclopropylamine using radio frequency (RF) capacitively coupled discharge. Normal human dermal fibroblasts were chosen for the monitoring of biological response to the properties of amine layers. As a superior technique for the label-free monitoring of the cell-surface interaction, coherence-controlled holographic microscopy (CCHM) was exploited. CCHM enables quantitative phase imaging. From such images, valuable morphological parameters of cells directly related to the cell dry mass can be extracted. Based on those parameters, viability of cells cultivated on the plasmatreated surfaces with ...
TY - JOUR. T1 - Marked reduction of alcohol dehydrogenase in keratoconus corneal fibroblasts. AU - Mootha, Venkateswara. AU - Kanoff, J. M.. AU - Shankardas, J.. AU - Dimitrijevich, S.. PY - 2009/4/10. Y1 - 2009/4/10. N2 - Purpose: To identify differentially expressed genes in keratoconus (KC) corneal fibroblasts. Methods: Stromal keratocytes (having a fibroblast morphology) from KC keratoplasty specimens and eye bank donor corneas were isolated and expanded using a serum containing medium. RNA was isolated from three KC fibroblast cultures and five eye bank donor cornea fibroblast cultures. The targets from the cultured fibroblasts were hybridized to the Affymetrix U133 Plus 2.0 microarrays. Western blot analyses of cell lysates were performed to examine protein levels of interest in the two groups. Protein levels of select differentially expressed genes were further examined by immunohistochemistry. Keratocyte staining of archived KC keratoplasty specimens were graded using a 0 to 3+ scale and ...
The addition of cardiac fibroblast-conditioned medium to purified cardiomyocyte cultures was associated with 1) cell hypertrophy, 2) vimentin expression in the presence of MyHC, and 3) markedly reduced spontaneous rhythmic contractions intrinsic to untreated cultured cardiomyocytes. These effects on cardiomyocyte structure and chronotropy in fibroblast-conditioned medium differed both in nature and time frame from the dedifferentiation or fetal gene program previously delineated in cardiomyocytes cultured under standard conditions (9, 11-14). For example, the progressive emergence of α-smooth muscle actin across all culture conditions was consistent with the dedifferentiation paradigm in contrast to vimentin expression specific to the fibroblast-conditioned medium (9, 14). These data suggest that cardiac fibroblasts introduced a soluble factor or factors into the medium that altered cardiomyocyte function and phenotype by either 1) a direct cell membrane or intracellular interaction or 2) ...
ATCC® Normal Adult Human Primary Dermal Fibroblasts, when grown in Fibroblast Basal Media supplemented with Fibroblast Growth Kit components, provide an ideal cell system to propagate dermal fibroblasts in either serum-free or low serum conditions. The cells are cryopreserved in their first passage to ensure the highest viability and plating efficiency. ATCC® Primary Cell Solutions™ cells, media, supplements and reagents are quality tested together to guarantee optimum performance and reliability.
Endogenous electric currents generated instantly at skin wounds direct migration of epithelial cells and are likely to be important in wound healing. Migration of fibroblasts is critical in wound healing. It remains unclear how wound electric fields guide migration of dermal fibroblasts. We report here that mouse skin wounds generated endogenous electric currents for many hours. Human dermal fibroblasts of both primary and cell-line cultures migrated directionally but slowly toward the anode in an electric field of 50-100 mV mm−1. This is different from keratinocytes, which migrate quickly to the cathode. It took more than 1 hour for dermal fibroblasts to manifest detectable directional migration. Larger field strength (400 mV mm−1) was required to induce directional migration within 1 hour after onset of the field. Phosphatidylinositol-3-OH kinase (PI3 kinase) mediates cathode-directed migration of keratinocytes. We tested the role of PI3 kinase in anode-directed migration of fibroblasts. ...
Cells invade tissues by sending out actin-rich protrusions called invadopodia that contain proteolytic enzymes that degrade the surrounding extracellular matrix (ECM). Fibroblasts without Snail1 formed fewer invadopodia and were less able to degrade the ECM. Rowe et al. transplanted the Snail1-deficient fibroblasts into chick embryos and found that they were completely unable to penetrate the basement membrane and the complex mix of ECM proteins beneath. Moreover, unlike wild-type fibroblasts, Snail1-deficient cells didnt stimulate the ingrowth of new blood vessels-another key function of fibroblasts during wound healing and tissue remodeling.. The team thinks that in addition to its role in EMT, Snail1 also acts as a master regulator of fibroblast function. In cancer cells, says author Grant Rowe, sustained Snail1 expression may not only cause a loss of epithelial markers but also promote tumor aggression by stimulating tissue invasion and angiogenesis.. ...
TY - JOUR. T1 - Heat Shock Protein 90 Inhibitor (17-AAG) Induces Apoptosis and Decreases Cell Migration/Motility of Keloid Fibroblasts. AU - Yun, In Sik. AU - Lee, Mi Hee. AU - Rah, Dong Kyun. AU - Lew, Dae Hyun. AU - Park, Jong Chul. AU - Lee, Won Jai. PY - 2015/7/4. Y1 - 2015/7/4. N2 - Background: The regulation of apoptosis, proliferation, and migration of fibroblasts is altered in keloids. The 90-kDa heat shock protein (heat shock protein 90) is known to play a key role in such regulation. Therefore, the authors investigated whether the inhibition of heat shock protein 90 in keloid fibroblasts could induce apoptosis and attenuate keloid fibroblast proliferation and migration. Methods: The authors evaluated heat shock protein 90 expression in keloid tissues with immunohistochemistry. The authors used cell viability [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays and annexin V/propidium iodide staining for apoptosis, a wound healing model and cell tracking system to ...
TY - JOUR. T1 - MicroRNA expression analysis of human skin fibroblasts treated with high-fluence light-emitting diode-red light. AU - Mamalis, Andrew. AU - Koo, Eugene. AU - Tepper, Clifford G. AU - Jagdeo, Jared. PY - 2019/1/1. Y1 - 2019/1/1. N2 - Skin fibrosis is a chronic debilitating feature of several skin diseases that lead to characteristic increases in dermal fibroblast proliferation and collagen deposition through upregulation in components of the transforming growth factor beta (TGF-B)/SMAD pathway. In contrast to ultraviolet phototherapy, high-fluence light-emitting diode-generated red light (HF-LED-RL, 633 ± 15 nm) is a safe, economic and non-invasive therapy with in vitro evidence that supports modulation of the key cellular characteristics involved in the pathogenesis of skin fibrosis. Limited data exists pertaining to the effects of HF-LED-RL on human skin fibroblast microRNA (miRNA). Herein, we explored the effects of HF-LED-RL on fibroblast miRNA levels using RNA-seq and miRNA ...
Endothelial progenitor cell (EPC) transplantation is a promising therapy for ischemic diseases such as ischemic myocardial infarction and hindlimb ischemia. However, limitation of EPC sources remains a major obstacle. Direct reprogramming has become a powerful tool to produce EPCs from fibroblasts. Some recent efforts successfully directly reprogrammed human fibroblasts into functional EPCs; however, the procedure efficacy was low. This study therefore aimed to improve the efficacy of direct reprogramming of human fibroblasts to functional EPCs. Human fibroblasts isolated from foreskin were directly reprogrammed into EPCs by viral ETV2 transduction. Reprogramming efficacy was improved by culturing transduced fibroblasts in hypoxia conditions (5 % oxygen). Phenotype analyses confirmed that single-factor ETV2 transduction successfully reprogrammed dermal fibroblasts into functional EPCs. Hypoxia treatment during the reprogramming procedure increased the efficacy of reprogramming from 1.21 ± 0.61 % in
TY - JOUR. T1 - Stromal fibroblasts support dendritic cells to maintain IL-23/Th17 responses after exposure to ionizing radiation. AU - Malecka, Anna. AU - Wang, Qunwei. AU - Shah, Sabaria. AU - Sutavani, Ruhcha V.. AU - Spendlove, Ian. AU - Ramage, Judith M.. AU - Greensmith, Julie. AU - Franks, Hester A.. AU - Gough, Michael J.. AU - Saalbach, Anja. AU - Patel, Poulam M.. AU - Jackson, Andrew M.. PY - 2016/8/1. Y1 - 2016/8/1. N2 - Dendritic cell function is modulated by stromal cells, including fibroblasts. Although poorly understood, the signals delivered through this crosstalk substantially alter dendritic cell biology. This is well illustrated with release of TNF-α/IL-1β from activated dendritic cells, promoting PGE2 secretion from stromal fibroblasts. This instructs dendritic cells to up-regulate IL-23, a key Th17-polarizing cytokine. We previously showed that ionizing radiation inhibited IL-23 production by human dendritic cells in vitro. In the present study, we investigated the ...
Helena is a Postdoctoral Researcher in the lab, working to define fibroblast the role of fibroblast sub-types in human skin wound healing. She conducted her PhD thesis in the lab, funded by a Department Scholarship. This work led to a patent application, and the lab was subsequently awarded an Imperial Confidence in Concept grant, and a grant from The Rosetrees Trust, enabling Helena to continue on her thesis work as a postdoctoral researcher. There are multiple fibroblast populations found in adult skin dermis, three of which we are particularly interested in; papillary fibroblasts, reticular fibroblasts and dermal papilla fibroblasts. In 2013 it was shown that these arise from a common cellular progenitor during development, yet acquire distinct identities in adult skin [1]. Using cell culture, immunofluorescence, confocal microscopy, RT-PCR and next generation sequencing approaches, Helena is defining the morphological, molecular and behavioural differences between these three fibroblast ...
Interstitial flow emanates from tumors into the microenvironment where it promotes tumor cell invasion. Fibroblasts are key constituents of the tumor stroma that modulate the mechanical environment by matrix remodeling and contraction. Here, we explore how interstitial fluid flow affects fibroblast-tumor cell interactions. Using a 3-dimensional invasion assay and MDA-MB-435S cells cocultured with dermal fibroblasts in a collagen matrix, we showed a synergistic enhancement of tumor cell invasion by fibroblasts in the presence of interstitial flow. Interstitial flow also drove transforming growth factor (TGF)-β1 and collagenase-dependent fibroblast migration, consistent with previously described mechanisms in which flow promotes invasion through autologous chemotaxis and increased motility. Concurrently, migrating fibroblasts enhanced tumor cell invasion by matrix priming via Rho-mediated contraction. We propose a model in which interstitial flow promotes fibroblast migration through increased TGF-β1
Plasma Fibroblast therapy is an elective, aesthetic, beauty procedure that can be offered as an alternative to laser, injections, and surgical therapies to tighten, rejuvenate. and improve the skins appearance.. Plasma Fibroblast therapy targets fibroblast cells. Fibroblasts are collagen and protein-producing cells in the dermis layer of skin which is just below your outermost skin layer. Fibroblasts play an important role in maintaining skin firmness and tightness, as well as, helping skin wounds heal.. Plasma Fibroblast therapy uses a pen-like device that discharges a high-frequency energy charge or arc. Your procedure will be performed using the Plamere™ Premium Plasma Pen (FDA registered). The plasma pens tip does not directly touch the skin, but instead releases a targeted arc just above the skins surface. This arc creates a tiny, micro-injury in the skins surface layer due to a reaction called sublimation.. ...
TY - JOUR. T1 - Low-dose of ionizing radiation enhances cell proliferation via transient ERK1/2 and p38 activation in normal human lung fibroblasts. AU - Kim, Cha Soon. AU - Kim, Jin Mo. AU - Nam, Seon Young. AU - Yang, Kwang Hee. AU - Jeong, Meeseon. AU - Kim, Hee Sun. AU - Lim, Young Khi. AU - Kim, Chong Soon. AU - Jin, Young Woo. AU - Kim, Joon. PY - 2007/9/27. Y1 - 2007/9/27. N2 - This study shows the human cellular responses and the mechanism of low-dose ionizing radiation in CCD 18 Lu cells, which are derived from normal human lung fibroblasts. Cell proliferation and viability assay were measured for the cells following γ-irradiation using trypan blue, BrdU incorporation, and Wst-1 assay. We also examined genotoxicity using a micronuclei formation assay. The activation of the MAPKs pathway was determined by Western blot analysis, and the siRNA system was used to inhibit the expression of ERK1/2 and p38. We found that 0.05 Gy of ionizing radiation stimulated cell proliferation and did not ...
Allogeneic cells are the most attractive source for cell transplantation, as the use of xenogeneic cells is hampered by safety concerns and the use of autologous cells involves practical difficulties. The immune rejection of allogeneic cells can be overcome by physical immunoprotection provided by polymer encapsulation. To study the variability of cell and donor sources, we compared different primary human cells as candidates for gene therapy-mediated delivery of human erythropoietin (hEpo). DARC-3.1 fibroblasts, MDX-01 fibroblasts, and ARPE-19 retinal pigment epithelial cells were encapsulated into polyethersulfone hollow fibers and implanted for 1 month in nude mice as well as in immunocompetent and FK506-immunosuppressed mice to test their in vivo resistance, with the assumption that xenogeneic conditions constitute a stringent model for human application. DARC-3.1 fibroblasts showed the best survival, prompting us to evaluate cell lineages from the same donor (DARC-3.2) or another donor (DARC-4.3
TY - JOUR. T1 - Expression of hydrogen peroxide and glutathione metabolizing enzymes in human skin fibroblasts derived from donors of different ages. AU - Keogh, Bart P.. AU - Allen, R. G.. AU - Pignolo, Robert. AU - Horton, Joseph. AU - Tresini, Maria. AU - Cristofalo, Vincent J.. PY - 1996/6. Y1 - 1996/6. N2 - We have examined the activities and mRNA abundance of two hydrogen peroxide metabolizing enzymes (glutathione peroxidase and catalase), glutathione concen tration, and the activities of several enzymes that influence glutathione concentration, including glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G-6-PD), and γ-glutamylcysteine synthetase (γ-GCS), in 29 skin fibroblast lines derived from donors ranging in age from 14 gestational weeks to 94 years of age. H2O2 metabolizing enzyme activities and mRNA abundances were greater in skin fibroblast cultures established from postnatal donors than in fetally derived cultures. There were no significant differences in either of ...
2015 Guo et al. A key feature of lung fibrosis is the accumulation of myofibroblasts. Interleukin 13 (IL-13) is a pro-fibrotic mediator that directly and indirectly influences the activation of myofibroblasts. Transforming growth factor beta (TGF-β) promotes the differentiation of fibroblasts into myofibroblasts, and can be regulated by IL-13. However, IL-13s downstream signaling pathways are not completely understood.We previously reported that the transcription factor Yin Yang 1 (YY1) is upregulated in fibroblasts treated with TGF-β and in the lungs of mice and patients with pulmonary fibrosis. Moreover, YY1 directly regulates collagen and alpha smooth muscle actin (a-SMA) expression in fibroblasts. However, it is not known if IL-13 regulates fibroblast activation through YY1 expression. We hypothesize that IL-13 upregulates YY1 expression through regulation of AKT activation, leading to fibroblast activation. In this study we found that YY1 was upregulated by IL-13 in lung fibroblasts in a ...
Abstract: : Purpose: Adenovirus infection of the cornea manifests as punctate epithelial keratitis, geographic epithelial erosions, and delayed-onset subepithelial corneal infiltrates. We have previously shown that (1)adenovirus type 19 (Ad19) infection of human corneal fibroblasts (HCF) induces expression of the neutrophil chemokine interleukin-8 (IL-8); (2) Ad19 infection of HCF induces tyrosine phosphorylation of the intracellular signaling protein c-src; and (3) phosphorylation of c-src is necessary for the expression of IL-8 by Ad19-infected HCF. These data suggest that Ad19 induces IL-8 expression in HCF by a signaling cascade involving c-src. In the experiments described herein, we sought to determine whether adenovirus infection of HCF might induce other host responses dependent on c-src associated signaling pathways. Methods: HCF were derived from donor corneas and infected for one hour with Ad19, or mock-infected with virus-free media. Parallel experiments were performed with the ...
TY - JOUR. T1 - A cell cycle study of the effects of Con A on synchronized mouse embryo fibroblasts. T2 - Arrest and dissociation between uptake of thymidine and DNA synthesis. AU - Mallucci, L.. AU - Dunn, M.. AU - Wells, V.. AU - Delia, D.. PY - 1980. Y1 - 1980. N2 - We have examined the effects of 50 μg ml-1 of Con A added to synchronized mouse embryo fibroblasts at different times during the cell cycle. We found that Con A caused arrest of growth not solely by preventing G1-G0 cells from entering the S-phase but also by exerting a G2 block. We also found that Con A, which prevented commencement of S-phase, did not arrest cells already in S from reaching the G2 stage but inhibited the S-phase associated process of thymidine uptake. The inhibition was greater when the Con A receptors were extensively clustered.. AB - We have examined the effects of 50 μg ml-1 of Con A added to synchronized mouse embryo fibroblasts at different times during the cell cycle. We found that Con A caused arrest of ...
Among cells present in the tumor microenvironment, activated fibroblasts termed cancer-associated fibroblasts (CAFs), play a critical role in the complex process of tumor-stroma interaction. CAFs, one of the prominent stromal cell populations in most types of human carcinomas, have been involved in tumor growth, angiogenesis, cancer stemness, extracellular matrix remodeling, tissue invasion, metastasis and even chemoresistance. During the past decade, these activated tumor-associated fibroblasts have also been involved in the modulation of the anti-tumor immune response on various levels. In this review, we describe our current understanding of how CAFs accomplish this task as well as their potential therapeutic implications.
During wound healing processes fibroblasts account for wound closure by adopting a contractile phenotype. One disease manifestation of COPD is emphysema which is characterized by destruction of alveolar walls and our hypothesis is that fibroblasts in the COPD lungs differentiate into a more contractile phenotype as a response to the deteriorating environment. Bronchial (central) and parenchymal (distal) fibroblasts were isolated from lung explants from COPD patients (n = 9) (GOLD stage IV) and from biopsies from control subjects and from donor lungs (n = 12). Tissue-derived fibroblasts were assessed for expression of proteins involved in fibroblast contraction by western blotting whereas contraction capacity was measured in three-dimensional collagen gels. The basal expression of rho-associated coiled-coil protein kinase 1 (ROCK1) was increased in both centrally and distally derived fibroblasts from COPD patients compared to fibroblasts from control subjects (p | 0.001) and (p | 0.01), respectively.
In this paper Claudia Manzoni studies how fibroblast cells from people with Parkinsons disease caused by mutations in LRRK2 ... Although the changes are quite subtle, there are differences between the way that fibroblasts that contain mutant LRRK2 respond ...
... untreated fibroblasts. Center: inflammatory stimulation hardly affects cell morphology. Right hand side: stimulation of wound ... Left hand side: untreated fibroblasts. Center: inflammatory stimulation hardly affects cell morphology. Right hand side: ...
Combined CSL and p53 downregulation promotes cancer-associated fibroblast activation.. *Cancer-Associated Fibroblasts: Their ... Cancer-associated fibroblasts (CAFs) are a major component of the cancer stroma. CAFs enhance the malignant features of nearby ... Resident tissue fibroblasts, bone marrow-derived mesenchymal stem cells, and hematopoietic stem cells are examples of possible ... Origins of cancer-associated fibroblast. Past studies have reported that many different cells could be the origin of CAFs. ...
... Stephen Knight stigh at Fri Nov 20 09:33:15 EST 1998 *Previous message: fibroblasts on beads ... Daniel Lottaz wrote: , , I intend to culture fibroblasts on beads prior to FACS-Analysis. Anyone , experience in such a ... Daniel Lottaz, Berne , e-mail: daniel.lottaz at Fibroblasts should not be difficult to culture on microcarrier ...
... poulain at poulain at Fri Aug 1 17:04:32 EST 1997 *Previous ... Hi! I am looking for a source of hygromycin-resistant fibroblasts to use as feeder layer to ES cells, preferably as a mouse ...
... such as endothelial cells and fibroblasts, have a prominent role in the progression, growth and spread of cancers. Fibroblasts ... such as endothelial cells and fibroblasts, have a prominent role in the progression, growth and spread of cancers. Fibroblasts ... Fibroblasts in cancer Nat Rev Cancer. 2006 May;6(5):392-401. doi: 10.1038/nrc1877. ... Fibroblasts are therefore a key determinant in the malignant progression of cancer and represent an important target for cancer ...
Biomedicine and the Centro Nacional de Análisis Genómico of the Center for Genomic Regulation explains how dermal fibroblasts ... the scientists observed that aged fibroblasts show a less defined molecular conformation compared to young fibroblasts and that ... Dermal fibroblasts are key for the production of collagen and other proteins that make up the dermis and that preserve the ... Tags: Adipocytes, Ageing, Biomedicine, Cell, Collagen, Fibroblast, Genomic, Newborn, Research, Scar, Skin ...
Cells that are found in the dermis (just under the skin) that help in healing wounds (to form scars and scar tissue). These cells are rapidly dividing, ...
Fibroblasts are the most common cells of connective tissue in animals. Fibroblasts have a branched cytoplasm surrounding an ... Fibroblasts, like the tumor-associated host fibroblasts (TAF), play a crucial role in immune regulation through TAF-derived ... The life span of a fibroblast, as measured in chick embryos, is 57 ± 3 days. Fibroblasts and fibrocytes are two states of the ... "Fibroblasts". Retrieved 16 August 2018. Weissman-Shomer P, Fry M (1975). "Chick embryo fibroblasts senscence in vitro: pattern ...
Telomere length predicts replicative capacity of human fibroblasts. R C Allsopp, H Vaziri, C Patterson, S Goldstein, E V ... Telomere length predicts replicative capacity of human fibroblasts. R C Allsopp, H Vaziri, C Patterson, S Goldstein, E V ... Telomere length predicts replicative capacity of human fibroblasts. R C Allsopp, H Vaziri, C Patterson, S Goldstein, E V ... When human fibroblasts from different donors are grown in vitro, only a small fraction of the variation in their finite ...
Generation and culture of mouse embryonic fibroblasts.. Lei Y1.. Author information. 1. Department of Diagnostic Sciences, ... The easy generation and physiological relevance of mouse embryonic fibroblasts (MEFs) have made them a powerful tool in ... fibroblasts, macrophages, dendritic cells, and lymphocytes. The extensive utilization of genetically manipulated animals in ...
The ability to repair tissues is essential for the survival of organisms. In chronic settings, the failure of the repair process to terminate results in overproduction of collagen, a pathology known as fibrosis, which compromises organ recovery and impairs function. The origin of the collagen-overproducing cell has been debated for years. Here we review recent insights gained from the use of lineage tracing approaches in several organs. The resulting evidence points toward specific subsets of tissue-resident mesenchymal cells, mainly localized in a perivascular position, as the major source for collagen-producing cells after injury. We discuss these findings in view of the functional heterogeneity of mesenchymal cells of the perivascular niche, which have essential vascular, immune, and regenerative functions that need to be preserved for efficient repair.. ...
... compared with CD38-expressing fibroblasts. Intrinsically, CAF-CD38 promoted migration of primary fibroblasts toward melanoma ... This study reports novel pro-tumorigenic functions for CD38 in cancer associated fibroblasts (CAFs). In vivo, CAF CD38 promotes ... Orthotopic co-implantation of CD38 deficient fibroblasts and B16F10 melanoma cells limited tumor size, ... of cancer-associated fibroblasts (CAFs). We previously reported in orthotropic/syngeneic mouse models that the stromal ...
Kit containing Dermal Fibroblasts (rabbit) and media. Cryo-preserved cells in medium containing 20% FBS and 10% DMSO at passage ... Dermal Fibroblasts, Mouse (BalbC) from CHEMICON. 2. Rabbit Anti-Aph-1aL, S Loop (92-115) Polyclonal Antibody, Unconjugated from ... Kit containing Dermal Fibroblasts (rabbit) and media. Cryo-preserved cells in medium containing 20% FBS and 10% DMSO at passage ...
GINTUIT (allogeneic cultured keratinocytes and fibroblasts in bovine collagen) cellular sheet NDC Code(s): 42606-004-01 ...
Regulation of cancer stem-like cells by cancer-associated fibroblasts [in Japanese] Murayama Takahiko , Gotoh Noriko ... Role of FAP positive cancer-associated fibroblasts in the esophageal squamous cell carcinoma microenvironment [in Japanese] ... Physical interaction of cancer cells and cancer associated fibroblasts [in Japanese] 加藤 琢哉 ... Mechanisms of cancer progression defined by the stiffness of stroma and the heterogeneity of cancer associated fibroblasts [in ...
Fibroblasts - Ellen Merfeld and Allison Schollmeyer by Allison Schollmeyer , This newsletter was created with Smore, an online ... Fibroblasts help to create connective tissue that supports, anchors and connects various parts of the body. The tissue holds ... Dermal Fibroblasts in the skin- *Generates connective tissue that allows the skin to recover from injury. ...
Like corneal fibroblasts, dermal fibroblast proliferation can be stimulated by the presence of fibroblast growth factor (FGF). ... For example, when a dermal fibroblast and a corneal fibroblasts are placed in the same concentrations of fibroblast growth ... Unlike other fibroblast cell types, dermal fibroblasts are far less likely to change into other cell types. ... Dermal fibroblasts require far higher concentrations of fibroblast growth factor (FGF) in order to undergo cell replication. ...
Phenotypic Plasticity of Fibroblasts during Mammary Carcinoma Development.. Elwakeel E1, Brüggemann M2, Fink AF1, Schulz MH3, ... Fibroblasts were identified as CD31− CD45− CD49f− CD326− Pdgfrb+ cells. Mock H&E images (scale bars: 100 µm) indicating tissue ... Colored arrowheads indicate fibroblasts co-expressing Foxo1 and Sirt1 (orange) or α-SMA and nuclear p65 (blue), and nuclear p65 ... FACS of fibroblasts from untransformed mammary gland, early and late PyMT tumors. Untransformed mammary glands (Ctrl) as well ...
Fibroblast Growth Factor A fibroblast is a connective-tissue cell of mesenchymal origin that secretes proteins and especially ... Fibroblast Growth Factor. A fibroblast is a "connective-tissue cell of mesenchymal origin that secretes proteins and especially ... FGFs initiate fibroblast proliferation. The original FGF molecule (now known as FGF-2 or FGF basic ) also induces proliferation ...
Further reports about: , Angiogenesis , ECM , EMT , Fibroblast , Snail1 , actin-binding proteins , blood vessel , epithelial- ... Angiogenesis »ECM »EMT »Fibroblast »Snail1 »actin-binding proteins »blood vessel »epithelial-specific genes »epithelial- ... Fibroblasts invade at a snails pace. 03.02.2009. Study finds Snail1 may spur cancer cells by stimulating tissue invasion and ... The team thinks that in addition to its role in EMT, Snail1 also acts as a master regulator of fibroblast function. In cancer ...
We found that fibroblasts from old donors exhibited an increase in rigidity of ∼60% with respect to cells of the youngest ... Here, we show that individual dermal fibroblasts also exhibit a significant increase in stiffness during aging in vivo. With ... The rheological analysis of fibroblast-populated collagen gels demonstrates that cell stiffening directly results in altered ... the laser-based optical cell stretcher we examined the viscoelastic biomechanics of dermal fibroblasts isolated from 14 human ...
... regulates the transition of normal fibroblasts to cancer-associated fibroblasts through histone methylation and promotes ... Stromal NNMT expression was necessary and sufficient for functional aspects of the cancer-associated fibroblast (CAF) phenotype ... MicroRNAs reprogram normal fibroblasts into cancer-associated fibroblasts in ovarian cancer. Cancer Discov. 2, 1100-1108 (2012 ... Proteomics reveals NNMT as a master metabolic regulator of cancer-associated fibroblasts. *Mark A. Eckert1. na1, ...
FGF, fibroblast growth factor; FGFR, FGF receptor; NA, not applicable; PDGFR, platelet-derived growth factor receptor; VEGFR ... The fibroblast growth factor (FGF) family nomenclature describes 23 members, although there are only 18 FGF receptor (FGFR) ... Fibroblast growth factors (FGFs) and their receptors control a wide range of biological functions, regulating cellular ... Fibroblast growth factors (FGFs) and their receptors (FGFRs) drive crucial developmental signalling pathways, which are ...
Taxol, a potent inhibitor of human HeLa and mouse fibroblast cell replication, blocked cells in the G2 and M phase of the cell ... Taxol inhibited the migration behavior of fibroblast cells, but these cells did not lose their ability to produce mobile ... Taxol stabilizes microtubules in mouse fibroblast cells. P B Schiff and S B Horwitz ...
Factors affecting fibroblast-to-myofibroblast transition during airway wall remodelling in bronchial asthma. FMT fibroblast-to- ... These features directly contribute to the higher stiffness of fibroblasts from AS subjects than that of fibroblasts from NA ... Gomes I, Mathur SK, Espenshade BM, Mori Y, Varga J, Ackerman SJ (2005) Eosinophil-fibroblast interactions induce fibroblast IL- ... fibronectin-induced fibroblast migration, and α-SMA and matrix contraction in pulmonary fibroblasts [139, 140, 141]. It also ...
Fibroblast growth factor 14 (IPR028284). Short name: FGF14 Family relationships *Fibroblast growth factor family (IPR002209) * ... Promiscuity of fibroblast growth factor receptors.. Bioessays 18 639-46 1996. Ornitz DM, Itoh N. Fibroblast growth factors.. ... This entry represents fibroblast growth factor 14 (FGF14), also known as fibroblast growth factor homologous factor 4. In mouse ... Fibroblast growth factors.. Genome Biol. 2 REVIEWS3005 2001. Wilkie AO, Morriss-Kay GM, Jones EY, Heath JK. Functions of ...
Fibroblasts ir šūna, kas sintezē ārpusšūnu matricu, kolagēnu, audu pamatu jeb stromu, kā arī šīm šūnām ir būtiska nozīme brūču ... "Fibroblast". Genetics Home Reference. U.S. National Library of Medicine. 2014-05-05. ... Saturs iegūts no "" ...
Pipette 15 ml of Fibroblast Growth Medium (116-500)* to a T-75 flask (SIAL0641).. * Keep the medium to surface area ratio at ... Take the Fibroblast Growth Medium (116-500) from the refrigerator. Decontaminate the bottle with 70% alcohol in a sterile hood. ... Take the Fibroblast Growth Medium (116-500) from the refrigerator. Decontaminate the bottle with 70% alcohol in a sterile hood. ... Pipette 30 ml of Fibroblast Growth Medium (116-500) to a T-175 flask (SIAL1080) (to be used in Section IV C Step 15.) ...
Malignant Neighbors Corrupt Stromal Fibroblasts Message Subject. (Your Name) has forwarded a page to you from Science Signaling ... B. Bierie, H. L. Moses, Under pressure: Stromal fibroblasts change their ways. Cell 123, 985-987 (2005). [PubMed] ... only mice also lacking p53 showed enhanced fibroblast proliferation in mesenchyme shortly (two months) after T121 induction. ...
  • A study published today in Cell by scientists at the Institute for Research in Biomedicine (IRB Barcelona) and the Centro Nacional de Análisis Genómico of the Center for Genomic Regulation (CNAG-CRG) explains how dermal fibroblasts age. (
  • Dermal fibroblasts are key for the production of collagen and other proteins that make up the dermis and that preserve the skin's function as a barrier. (
  • Kit containing Dermal Fibroblasts (rabbit) and media. (
  • Dermal Fibroblasts are responsible for producing the extracellular matrix forming the connective tissue of the skin, and play a crucial role during wound healing. (
  • Dermal fibroblasts are cells within the dermis layer of skin which are responsible for generating connective tissue and allowing the skin to recover from injury. (
  • Using organelles (particularly the rough endoplasmic reticulum), dermal fibroblasts generate and maintain the connective tissue which unites separate cell layers. (
  • Furthermore, these dermal fibroblasts produce the protein molecules including laminin and fibronectin which comprise the extracellular matrix. (
  • Dermal fibroblasts are derived from mesenchymal stem cells within the body. (
  • Like corneal fibroblasts, dermal fibroblast proliferation can be stimulated by the presence of fibroblast growth factor (FGF). (
  • One example of further differentiation of dermal fibroblasts is that upon injury, dermal fibroblasts can give rise to myofibroblasts, fibroblast cells with smooth muscle characteristics. (
  • Dermal cells differentiate into myofibroblasts by altering their actin gene expression (which is silenced in dermal fibroblasts). (
  • When dermal fibroblasts express actin, the cells can slowly contract. (
  • Unlike other fibroblast cell types, dermal fibroblasts are far less likely to change into other cell types. (
  • For example, when a dermal fibroblast and a corneal fibroblasts are placed in the same concentrations of fibroblast growth factor, dermal fibroblast will not differentiate or change. (
  • Furthermore, dermal fibroblasts are less likely to replicate in either in vivo and in vitro environments than are other fibroblast types. (
  • Dermal fibroblasts require far higher concentrations of fibroblast growth factor (FGF) in order to undergo cell replication. (
  • Dermal fibroblasts are responsible for creating the ECM which organizes the stratified squamous epithelial cells of the epidermis into a unified tissue. (
  • Furthermore, dermal fibroblasts create long fibrous bands of connective tissue which anchor the skin to the fascia of the body. (
  • Therefore, without dermal fibroblasts, the largest and heaviest organ would not tightly adhere to body's frame. (
  • Since dermal fibroblasts play a critical role in wound healing, researchers are attempting to generate mature dermal fibroblasts to repair second and third degree burns. (
  • When the body sustains a third degree burn, the skin's dermal layer is completely destroyed by heat (and the all fibroblast cells within the wound site perish). (
  • Therefore, without dermal fibroblasts the skin cannot properly recover from injury. (
  • Yet, by differentiating mesenchymal stem cells from other regions of the body and injecting them into the wound site, scientists can restore dermal fibroblasts to burned regions of the body. (
  • Transcriptomics evaluation of hexavalent chromium toxicity in human dermal fibroblasts. (
  • In order to understand the mechanisms of dermal toxicity induced by hexavalent chromium, global gene expression profiling of human dermal fibroblasts exposed to potassium dichromate was performed. (
  • Induction of apoptosis and oxidative stress in the dermal fibroblasts in response to their exposure to chromium was independently confirmed by additional experiments. (
  • In new research published in 2014's edition of the British Journal of Cancer(2), genetically engineered melanoma cell lines and xenograft mouse models were used to investigate how BRAF V600E affected cytokine (IL-1β, IL-6, and IL-8) and matrix metalloproteinase-1 (MMP-1) expression in tumour cells and in human dermal fibroblasts. (
  • This study suggests a pathogenic role of scleroderma-specific autoantibodies to directly induce pro-fibrotic activation in human dermal fibroblasts. (
  • Identification of regulators of the myofibroblast phenotype of primary dermal fibroblasts from early diffuse systemic sclerosis (dSSc) patients. (
  • Our results demonstrated the value of carefully-phenotyped SSc dermal fibroblasts as a platform for SSc target and drug discovery. (
  • Contractility of single human dermal myofibroblasts and fibroblasts. (
  • We have compared the contractile properties of single human dermal fibroblasts and human dermal myofibroblasts by culturing them on flexible silicone elastomers. (
  • Primary dermal fibroblasts obtained from 14 patients with scleroderma and from 4 healthy adult volunteers were studied. (
  • First-authored by IRB Barcelona PhD student Marion Salzer, the study demonstrates that, during ageing, skin fibroblasts start to acquire many traits that are characteristic of adipocytes (fat cells). (
  • Stiffening of human skin fibroblasts with. (
  • With the objective of investigating whether metabolic abnormalities would be detected in peripheral non-neuronal cells, we began assessing key metabolic parameters in skin fibroblasts of these patients. (
  • IMR-91 diploid male fetal skin fibroblasts cultures are also available at low, intermediate, and high population doublings. (
  • Antibodies against specific extractable nuclear antigens (ENAs) as diagnostic and prognostic tools and inducers of a profibrotic phenotype in cultured human skin fibroblasts: are they functional? (
  • I've been trying to isolate skin fibroblasts from rat's skin and used different methods and protocols which wasnt successful, the skin has trouble attaching to the plastic surface (now i'm trying to isolate them from rabbit's skin ) also i\m not sure what serum concentration i have to add 10% or 20% its different depending on the protocol. (
  • Moreover, the concentration of hepatocyte growth factor (HGF) cytokine in the conditioned medium of H-CAFs was higher than conditioned medium from normal skin fibroblasts (NSFs). (
  • FGFs initiate fibroblast proliferation. (
  • Fibroblast growth factors (FGFs) and their receptors control a wide range of biological functions, regulating cellular proliferation, survival, migration and differentiation. (
  • Whereas all TgAPT 121 prostates showed enhanced epithelial cell proliferation before tumor development, only mice also lacking p53 showed enhanced fibroblast proliferation in mesenchyme shortly (two months) after T 121 induction. (
  • We studied the effect of morphine, an active metabolite of heroin, on the proliferation of kidney fibroblasts. (
  • 0.001) the proliferation of kidney fibroblasts (control, 67.5 +/- 2.0 vs. morphine, 112.2 +/- 10.1 x 10(4) cells/well). (
  • We speculate that morphine-induced kidney fibroblast proliferation may be mediated through the activation of early growth related genes, whereas morphine induced kidney fibroblast apoptosis may be mediated through the generation of p53. (
  • As noted "The injured dermis is also repaired by the recruitment and proliferation of fibroblasts producing extracellular matrix and keratinocyte growth promoting factors. (
  • PHD2 siRNA treatment not only increased the expression of HIF1α and VEGFa, but also improved the fibroblast proliferation. (
  • Therefore proliferation of skin fibroblast along with differentiation of stem cells in the skin tissue is the best method for healing. (
  • To study whether this TRPM7-like current promotes fibroblast proliferation, we designed siRNA specifically targeting human TRPM7. (
  • 3,5 Proliferation of cardiac fibroblasts and deposition of collagen are directly associated with both systolic and diastolic (especially the latter) heart failure. (
  • Activation of the renin-angiotensin system with synthesis and release of angiotensin II (Ang II) is a key feature of hypertension and myocardial ischemia, and both conditions lead to cardiac remodeling comprising myocyte hypertrophy and fibroblast proliferation. (
  • 8 AT 1 receptors are widely present on cardiac fibroblasts, and Ang II via AT 1 activation mediates fibroblast proliferation and ECM production. (
  • Cancer-associated fibroblasts from hepatocellular carcinoma promote malignant cell proliferation by HGF secretion. (
  • Cancer-associated fibroblasts (CAFs) are reported to support tumorigenesis by stimulating angiogenesis, cancer cell proliferation, and invasion in most solid tumors. (
  • Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. (
  • In this paper Claudia Manzoni studies how fibroblast cells from people with Parkinson's disease caused by mutations in LRRK2 react to starvation . (
  • Although the changes are quite subtle, there are differences between the way that fibroblasts that contain mutant LRRK2 respond to being starved - suggesting that there may be changes in the way that these cells regulate a key process called autophagy (a term which comes from the greek meaning to eat yourself, and is one of the ways that cells get rid of waste and recycle proteins and organellles). (
  • Cancer cells that were cultured with CAFs had down-regulated E-cadherin expression compared to cancer cells that were cultured with normal fibroblasts. (
  • Resident tissue fibroblasts, bone marrow-derived mesenchymal stem cells, and hematopoietic stem cells are examples of possible predecessors of CAFs. (
  • One method involves cancer cells reprogramming resident tissue fibroblasts to become CAFs, using small non-coding RNA molecules known as microRNAs or miRNAs (such as miR-31 and miR-214). (
  • Finally, bone marrow-derived mesenchymal stem cells (BM-MSCs) can alter secreted transforming growth factor-β1 (TGF-β1), which promotes the formation of CAFs from fibroblasts. (
  • I am looking for a source of hygromycin-resistant fibroblasts to use as feeder layer to ES cells, preferably as a mouse that carries the bacterial gene as a transgene. (
  • Tumours are known as wounds that do not heal - this implies that cells that are involved in angiogenesis and the response to injury, such as endothelial cells and fibroblasts, have a prominent role in the progression, growth and spread of cancers. (
  • Fibroblasts are associated with cancer cells at all stages of cancer progression, and their structural and functional contributions to this process are beginning to emerge. (
  • Fibroblasts are large, flat, elongated (spindle-shaped) cells possessing processes extending out from the ends of the cell body. (
  • Fibroblasts produce tropocollagen, which is the forerunner of collagen , and ground substance , an amorphous gel-like matrix that fills the spaces between cells and fibres in connective tissue. (
  • Fibroblasts appear to play an important role in wound healing, and this activity is thought to be regulated by cells known as fibrocytes residing in the tissue stroma. (
  • The innate immune system is evolutionarily conserved and shared by a wide spectrum of cells, including epithelial cells, endothelial cells, fibroblasts, macrophages, dendritic cells, and lymphocytes. (
  • Orthotopic co-implantation of CD38 deficient fibroblasts and B16F10 melanoma cells limited tumor size, compared with CD38-expressing fibroblasts. (
  • Intrinsically, CAF-CD38 promoted migration of primary fibroblasts toward melanoma cells. (
  • Fig. 2: CD38 in fibroblasts regulates migration of fibroblasts and B16F10 melanoma cells. (
  • The TME contains multiple types of stromal cells, cancer - associated fibroblasts (CAFs), Tumor endothelial cells (TECs), tumor- associated adipocytes (TAAs), tumor- associated macrophages (TAMs) and others. (
  • Cancer-associated fibroblasts (CAFs) in the tumor microenvironment contribute to all stages of tumorigenesis and are usually considered to be tumor-promoting cells. (
  • The conversion of epithelial cells into fibroblast-like mesenchymal cells is a critical event in both normal development and cancer. (
  • Moreover, unlike wild-type fibroblasts, Snail1-deficient cells didn't stimulate the ingrowth of new blood vessels-another key function of fibroblasts during wound healing and tissue remodeling. (
  • Taxol, a potent inhibitor of human HeLa and mouse fibroblast cell replication, blocked cells in the G2 and M phase of the cell cycle and stabilized cytoplasmic microtubules. (
  • Taxol inhibited the migration behavior of fibroblast cells, but these cells did not lose their ability to produce mobile surface projections such as lamellipodia and filopodia. (
  • Change Fibroblast Growth Medium ( 116-500 ) every other day until the cells reach 60% confluency. (
  • Fibroblasts are the most common cells of connective tissue in animals. (
  • Fibroblasts can also migrate slowly over substratum as individual cells, again in contrast to epithelial cells. (
  • While epithelial cells form the lining of body structures, it is fibroblasts and related connective tissues which sculpt the "bulk" of an organism. (
  • Fibroblasts and fibrocytes are two states of the same cells, the former being the activated state, the latter the less active state, concerned with maintenance and tissue metabolism. (
  • Like other cells of connective tissue, fibroblasts are derived from primitive mesenchyme. (
  • In certain situations, epithelial cells can give rise to fibroblasts, a process called epithelial-mesenchymal transition (EMT). (
  • Receptors on the surface of fibroblasts also allow regulation of hematopoietic cells and provide a pathway for immune cells to regulate fibroblasts. (
  • The connective tissue cells known as fibroblasts are vitally important for our recovery from injury. (
  • The fibroblasts are 'activated' and, because of this activation, they recruit immune cells and affect blood vessels," adds Prof. Erez. (
  • Repression of a single protein in ordinary fibroblasts is sufficient to directly convert the cells - abundantly found in connective tissues - into functional neurons. (
  • Confocal micrograph of a primary human fibroblast cell grown in culture stained blue for actin, a highly abundant protein that makes up the cytoskeleton of cells. (
  • Here, we describe in detail lenti-virus-based procedure for direct conversion of human fibroblasts to hepatocytes (hiHep cells) in vitro. (
  • By creating the extracellular matrix between the dermis and epidermis, fibroblasts allow the epithelial cells of the epidermis to affix the matrix, thereby allowing the epidermal cells to effectively join together to form the top layer of the skin. (
  • After examining the CD markers of the fibroblast cells, researchers at BioMed Central discovered that these cell lack "distinctive markers" confirming that these cells can be further differentiated. (
  • As noted by Dr. J. Lewis and Dr. A. Johnson authors of Microbiology of the Cell, "fibroblasts from the skin are different" and behave differently from other fibroblast cells to identical chemical stimuli. (
  • Without fibroblasts, the wound site cannot regenerate extracellular matrix and epidermis skin cells cannot proliferate over the wound site. (
  • Microarray analysis of the gene expression profile in the fibroblasts treated with potassium dichromate identified significant differential expression of approximately 1,200 transcripts compared with the control cells. (
  • Propagation of Pluripotent Mouse Embryonic Stem (ES) Cells Protocol This protocol describes the culture of embryonic stem (ES) cells using mitotically inactivating primary mouse embryonic fibroblast (MEF) cells as a feeder layer (preparation described in Preparation of Mouse Embryonic Fibroblast (MEF) Feeder Plates). (
  • The role of cyclins in controlling G1 progression in mammalian cells was tested by construction of fibroblasts that constitutively overexpress human cyclin E. This was found to shorten the duration of G1, decrease cell size, and diminish the serum requirement for the transition from G1 to S phase. (
  • It was also found that the conditioned medium from the BRAF V600E melanoma cells activated the stromal fibroblasts, inducing expression of SDF-1 and its receptor CXCR4. (
  • To investigate the role of mast cells (MC) and their fibrogenic growth factors in silicosis, we performed quantitative immunohistochemistry for MC tryptase and for basic fibroblast growth factor (bFGF) in lung tissue from silicotic and control subjects. (
  • Desmoplasia, composed of extracellular matrix (ECM), cancer-associated fibroblasts (CAFs), and infiltrating immune and endothelial cells, acts as a biophysical barrier to hinder chemotherapy and actively contributes to tumor progression and metastasis. (
  • Fibroblasts are cells that synthesize the extracellular matrix and collagen and play a critical role in wound healing and maintenance of healthy skin. (
  • Each single use container of autologous cultured fibroblasts has approximately 20 million cells aseptically processed and suspended in 1 mL of sterile, buffered Dulbecco's Modified Eagles Medium (DMEM). (
  • Consistent with the decreased current amplitude, Ca 2+ influx in siRNA treated fibroblasts was significantly smaller than those of control fibroblasts, further suggesting that TRPM7-like current contributes to calcium signaling in these cells. (
  • Furthermore, UV treated invasive S. flexneri, which lose the ability to invade cells, failed to induce IFN production in fibroblasts after bacterial challenge. (
  • Among cells present in the tumor microenvironment, activated fibroblasts termed cancer-associated fibroblasts (CAFs), play a critical role in the complex process of tumor-stroma interaction. (
  • In this study, we examined whether exosomes produced by cancer cells could transmit information to normal stromal fibroblasts and trigger a cellular response. (
  • TGF-β remains among the key factors responsible for the development of a myofibroblastic phenotype from a variety of precursor cells, including fibroblasts ( 15 ). (
  • GBA1 activities in both total lysate and PM of GD fibroblasts were low, and their relative percentages were similar to those of control cells. (
  • Fibroblast lines are derived from cells that synthesise the extracellular matrix and collagen, produce the structural framework for animal tissues, and play a critical role in wound healing. (
  • Five vials of irradiated mouse embryonic fibroblasts are provided with 6 x 10 6 cells in each vial. (
  • Human Pluripotent Stem Cells Cultured on Mouse Embryonic Fibroblasts Express Pluripotent Markers SSEA-4, Oct-3/4, Oct-4A, and E-Cadherin. (
  • BG01V Human Embryonic Stem Cells Cultured on Irradiated Mouse Embryonic Fibroblasts Demonstrate a Phenotype that is Consitent with Pluripotency. (
  • Tissue resident mesenchymal cells, including fibroblasts, exhibit disease and site-specific phenotypes, which can become epigenetically imprinted after exposure to inflammatory signals. (
  • Advancing understanding of the diversity and biology of fibroblast subsets presents an opportunity to develop precision therapeutic targeting of cells driving pathology in inflammatory arthritis. (
  • Your attachment problems with fibroblasts may not be due to the surface at all, but rather the amphotericin B, it is quite cytotoxic to all eukaryotic cells, just more so to fungi/yeast. (
  • The method employed a protein list based on 759 protein products of genes identified by RNA profiling from our previous study, comparing fibroblasts with differential growth-modulating effect on human cancers cells, and their first neighbors in the human protein interactome. (
  • Cells from a line of transformed quail fibroblasts (QT-6) were transfected with cDNAs coding for subunits of the mouse muscle nicotinic ACh receptor (AChR). (
  • Other investigators and we have shown that fibroblasts derived from IPF lungs display characteristics of senescent cells, and that dysregulated activation of the transcription factor signal transducer and activator of transcription 3 (STAT3) correlates with IPF progression. (
  • When human fibroblasts from different donors are grown in vitro, only a small fraction of the variation in their finite replicative capacity is explained by the chronological age of the donor. (
  • We also found that fibroblasts from Hutchinson-Gilford progeria donors had short telomeres, consistent with their reduced division potential in vitro. (
  • In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state," Nature , vol. 448, no. 7151, pp. 318-324, 2007. (
  • Huang P., Sun L., Zhang L., Hui L. (2019) Conversion of Fibroblasts to Hepatocytes In Vitro. (
  • Autologous cultured fibroblast is derived from in vitro expansion of fibroblasts harvested from the patient's normal skin. (
  • During the last decade it has become clear that periodontal ligament fibroblasts may contribute to the in vitro differentiation of osteoclasts. (
  • In vitro experiments have demonstrated that periodontal ligament fibroblasts adapt to bacterial and mechanical stimuli by synthesizing higher levels of osteoclastogenesis-stimulating molecules. (
  • Modeling pain in vitro using nociceptor neurons reprogrammed from fibroblasts. (
  • Using fibroblasts from patients with familial dysautonomia (hereditary sensory and autonomic neuropathy type III), we found that the technique was able to reveal previously unknown aspects of human disease phenotypes in vitro. (
  • Using an in vitro model, primary human lung fibroblasts were stimulated with biomass smoke extract (BME), specifically investigating hardwood and softwood types, and human rhinovirus-16 for 24 h. (
  • Stromal NNMT expression was necessary and sufficient for functional aspects of the cancer-associated fibroblast (CAF) phenotype, including the expression of CAF markers and the secretion of cytokines and oncogenic extracellular matrix. (
  • Fibroblast-to-myofibroblast transition requires a combination of several types of factors, the most important of which are divided into humoural and mechanical factors, as well as certain extracellular matrix proteins. (
  • A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework (stroma) for animal tissues, and plays a critical role in wound healing. (
  • The main function of fibroblasts is to maintain the structural integrity of connective tissues by continuously secreting precursors of the extracellular matrix. (
  • Fibroblasts secrete the precursors of all the components of the extracellular matrix, primarily the ground substance and a variety of fibers. (
  • Fibroblasts, like the tumor-associated host fibroblasts (TAF), play a crucial role in immune regulation through TAF-derived extracellular matrix (ECM) components and modulators. (
  • Here we demonstrate that respiratory viral infection induces distinct fibroblast activation states, which we term extracellular matrix (ECM)-synthesizing, damage-responsive and interferon-responsive states. (
  • fibroblasts (CAFs) are a major component of the cancer stroma. (
  • The conversion of CAFs from normal fibroblasts can occur in many ways. (
  • More recent research has discovered that the conversion of normal fibroblasts into CAFs involves the alteration of p53 from tumor-suppressive actions to tumor-supportive actions. (
  • Primary and metastatic melanoma progression are supported by a local microenvironment comprising, inter alia , of cancer-associated fibroblasts (CAFs). (
  • BACKGROUND:The tumor microenvironment, including cancer - associated fibroblasts (CAFs), plays various clinical roles in cancer growth. (
  • Generation and culture of mouse embryonic fibroblasts. (
  • The easy generation and physiological relevance of mouse embryonic fibroblasts (MEFs) have made them a powerful tool in discovering novel signaling pathways, investigating regulatory networks, and exploring biochemical profiling of protein complexes involved in innate immune responses. (
  • Protocols and information related to mouse embryonic fibroblasts. (
  • The researchers found that the same protocol worked with embryonic fibroblasts. (
  • Mitotically inactive mouse embryonic fibroblasts (MEFs) support the growth and maintenance of stem cell pluripotency by secreting necessary soluble factors and by providing a substrate for stem cell attachment. (
  • Mouse embryonic fibroblasts (MEF) were isolated from E13.5 CF1 embryos after removal of brain and visceral tissue. (
  • BG01V human embryonic stem cell colonies cultured on Irradiated Mouse Embryonic Fibroblasts (Catalog # PSC001) were analyzed for markers of pluripotency after 3 passages. (
  • Treatment of basic fibroblast growth factor (bFGF) with organic disulfides, preferably glutathione disulfide, or with inorganic compounds of similar function results in a bFGF composition of enhanced stability and resistance to multimerization. (
  • These formulations provide a stabilized basic fibroblast growth factor (bFGF) which is less susceptible to oxidation or metal-induced aggregation by including an amount of a chelating agent effective to stabilize the bFGF. (
  • 1. A stabilized basic fibroblast growth factor pharmaceutical formulation consisting essentially of a basic fibroblast growth factor (bFGF) and a chelating agent or a pharmaceutically acceptable salt thereof in an amount effective to stabilize said bFGF. (
  • 12. The stabilized bFGF formulation of claim 1 wherein said basic fibroblast growth factor is from a mammalian source. (
  • 13. The stabilized bFGF formulation of claim 10 which is human basic fibroblast growth factor. (
  • An isolated DNA sequence encoding an angiogenic factor protein consisting of a single-polypeptide-chain protein having at least one active site possessing mitotic and chemotactic activity and the ability to stimulate protease synthesis, wherein said protein consists of the amino acid sequence: ##STR1## In a preferred embodiment, the DNA sequence encodes basic fibroblast growth factor (bFGF). (
  • Basic fibroblast growth factor (bFGF) has been implicated in the brain's trophic response to injury. (
  • Addition of a single dose of 10 ng/ml basic fibroblast growth factor (bFGF) to the culture medium induced an average increase of sixfold in the numbers of neurons expressing opsin. (
  • Fibroblast , the principal active cell of connective tissue . (
  • Fibroblasts help to create connective tissue that supports, anchors and connects various parts of the body. (
  • Stretch-induced cell body expansion ex vivo was inhibited by colchicine and cytochalasin D. The dynamic, cytoskeleton-dependent responses of fibroblasts to changes in tissue length demonstrated in this study have important implications for our understanding of normal movement and posture, as well as therapies using mechanical stimulation of connective tissue including physical therapy, massage, and acupunc-ture. (
  • Using FGF stimulate fibroblast activity is a more effective means of sealing tissue than current tissue sealants due to the robust nature of collagen which makes up connective tissue. (
  • Vimentin Expression in Tumor Microenvironment Predicts Survival in Pancreatic Ductal Adenocarcinoma: Heterogeneity in Fibroblast Population. (
  • Cancer - associated fibroblasts (CAF) constitute a major component of the tumor microenvironment. (
  • These results show that BRAF V600E plays a key role in activating the stroma and supports the theory that there is a mechanistic link between BRAF V600E and MMP-1 in mediating melanoma progression and in activating adjacent fibroblasts in the tumour microenvironment. (
  • By producing ECM-remodelling enzymes-in particular the ECM protease ADAMTS4-and inflammatory cytokines, damage-responsive fibroblasts modify the lung microenvironment to promote robust immune cell infiltration at the expense of lung function. (
  • Increasing evidence indicates the importance of the tumor microenvironment, in particular cancer-associated fibroblasts, in cancer development and progression. (
  • Reactive oxygen species (ROS) also promote the conversion of fibroblasts into highly migrating myofibroblasts via the accumulation of the hypoxia-inducible factor-1α (HIF-1α) transcription factor and the CXCL12 chemokine. (
  • The findings, which could have far-reaching implications for the development of new treatments for neurodegenerative diseases like Huntington s, Parkinson s and Alzheimer s, will be published online in advance of the January 17 issue of the journal Cell ( 'Direct Conversion of Fibroblasts to Neurons by Reprogramming PTB-Regulated MicroRNA Circuits' ). (
  • They were then able to identify that the inflammation pathway is unregulated in cancer-associated fibroblasts, as compared with fibroblasts isolated from normal mammary glands. (
  • Phenotypic fibroblast-to-myofibroblast transition represents one of the primary mechanisms by which myofibroblasts arise in fibrotic lung tissue. (
  • Myofibroblasts can also be derived from non-fibroblast sources. (
  • We found that some cancer-derived exosomes could trigger elevated α-smooth muscle actin expression and other changes consistent with the process of fibroblast differentiation into myofibroblasts. (
  • To gain more insight into these aspects of exosome function, we chose to focus on a biological function of TGF-β that is of major importance in health and disease conditions: the induction of fibroblast differentiation to myofibroblasts. (
  • The mean contractile force produced by myofibroblasts (2.2 microN per cell) was not significantly different from that generated by fibroblasts (2.0 microN per cell) when cultured on a substrata with a low elastomer stiffness. (
  • Forces produced by fibroblasts were unaffected by increases in elastomer stiffness, but forces measured for myofibroblasts increased to a mean value of 4.1 microN/cell. (
  • This was associated with a higher proportion of myofibroblasts being able to produce wrinkles on elastomers of high stiffness compared to fibroblasts. (
  • We discuss the force measurements at the single cell level, for both fibroblast and myofibroblasts, in relation to the proposed role of myofibroblasts in wound healing and pathological contractures. (
  • were surprised to see that normal fibroblasts retained many mesenchymal characteristics when Snail1 was removed. (
  • Conversely, fibroblasts in some situations may give rise to epithelia by undergoing a mesenchymal to epithelial transition (MET) and organizing into a condensed, polarized, laterally connected true epithelial sheet. (
  • These include vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), stromal cell-derived factor 1 (SDF-1), fibroblast growth factor (FGF), and interleukin-6 (IL-6). (
  • The loss of p53 allows the fibroblasts to overcome senescence, enhances expression of CAF effectors, and promotes stromal and cancer cell expansion. (
  • B. Bierie, H. L. Moses, Under pressure: Stromal fibroblasts change their ways. (
  • 14C-Acetate incorporation into cholesterol of these fibroblasts was 27.8 +/- 9.4% that observed in normal fibroblasts, and the reduced cholesterol synthesis was confirmed by measuring the activity of the rate-limiting enzyme HMGCoA reductase which averaged 6.64 +/- 2.50 nmol/h/mg protein in the patient's fibroblasts compared to 14.70 +/- 0.69 nmol/h/mg protein in the control fibroblasts. (
  • In sharp contrast to control fibroblasts, which displayed predominantly cytoplasmic localization of SMAD3/4 in the absence of exogenous TGFβ, in scleroderma fibroblasts SMAD3 and SMAD4 consistently showed elevated nuclear localization. (
  • Fibroblast growth factors (FGFs) that signal through FGF receptors (FGFRs) regulate fundamental developmental pathways, controlling events such as mesoderm patterning in the early embryo [ 1 ] through to the development of multiple organ systems. (
  • Fibroblast growth factors (FGFs) [ PMID: 2549857 , PMID: 3072709 ] are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [ PMID: 1705486 , PMID: 8760337 ]. (
  • Fibroblast growth factors (FGFs) and their receptors (FGF receptors) constitute a signalling system conserved throughout animal evolution. (
  • Affinity for fibroblast growth factors (FGFs) is increased by heparan sulfate glycosaminoglycans that function as coreceptors. (
  • In the May 26 Nature online, scientists at Stanford University in Palo Alto, California, describe how to go directly from human fibroblasts to neurons, skipping the iPS stage altogether. (
  • We identified five transcription factors that reprogram mouse and human fibroblasts into noxious stimulus-detecting (nociceptor) neurons. (
  • In my cultures (DRG neurons), I consider fibroblasts a contaminant, but I can tell you that with Poly-L-Lysine and/or Laminin, they attach just fine. (
  • SMAD signaling may be a mechanism contributing to the characteristic phenotype of scleroderma fibroblasts and playing a role in the pathogenesis of fibrosis. (
  • The authors did find, however, that many genes important for cell motility, such as actin-binding proteins and matrix metalloproteinases, were expressed at lower levels in fibroblasts lacking Snail1. (
  • transplanted the Snail1-deficient fibroblasts into chick embryos and found that they were completely unable to penetrate the basement membrane and the complex mix of ECM proteins beneath. (
  • Fibroblast growth factors are heparin-binding proteins and interactions with cell-surface-associated heparan sulfate proteoglycans have been shown to be essential for FGF signal transduction. (
  • The heparin-binding (fibroblast) growth factor family of proteins. (
  • The fibroblast growth factors (FGF) are a family of cell signalling proteins that are involved in a wide variety of processes, most notably as crucial elements for normal development. (
  • A mitogenic growth factor activity was found in pituitary extracts by Armelin in 1973 [12] and further work by Gospodarowicz as reported in 1974 described a more defined isolation of proteins from cow brain extract which, when tested in a bioassay that caused fibroblasts to proliferate , led these investigators to apply the name "fibroblast growth factor. (
  • These independently discovered proteins were eventually demonstrated to be the same sets of molecules, namely FGF1, HBGF-1 and ECGF-1 were all the same acidic fibroblast growth factor described by Gospodarowicz, et al. (
  • These 2,654 proteins were analyzed in the Human Protein Atlas online database by comparing their immunohistochemical expression patterns in normal versus tumor-associated fibroblasts. (
  • Subsequent analysis identified fibroblast growth factor (FGF)-1 as an adipogenic factor produced by MVECs. (
  • Following tissue injury, fibroblasts migrate to the site of damage, where they deposit new collagen and facilitate the healing process. (
  • Fibroblasts make collagen fibres, glycosaminoglycans, reticular and elastic fibers. (
  • Angiotensin II (Ang II)-mediated stimulation of fibroblast growth and collagen type I synthesis is believed to be an important component of the cardiac remodeling process in hypertension and chronic ischemia. (
  • Ang II-mediated oxidative stress could be important in enhanced fibroblast growth and collagen formation. (
  • Accordingly, we postulated that the PPAR-γ ligand, pioglitazone, which is known to modulate oxidative stress, would alter Ang II-induced formation of collagen type I in cardiac fibroblasts. (
  • Thus, pioglitazone attenuates Ang II-mediated collagen type I synthesis in cardiac fibroblasts. (
  • 3,4 Fibroblasts are the major source of collagen in the myocardium. (
  • During the past decade, these activated tumor-associated fibroblasts have also been involved in the modulation of the anti-tumor immune response on various levels. (
  • According to the study, the inflammatory response of fibroblasts not only supports local tumor growth in the breast, but it also creates a hospitable niche for metastatic growth in the lungs. (
  • Functionally distinct fibroblast subsets mediate inflammation or tissue damage in inflammatory arthritis. (
  • Using murine models of inflammatory arthritis and synovial biopsies from patients with osteoarthritis or resolving and persistent rheumatoid arthritis (RA), Croft and colleagues identify and describe the biology of distinct fibroblast subsets responsible for mediating either inflammation or destruction of joint tissues. (
  • In contrast, transfer of FAPα + THY1 + fibroblasts induced severe and persistent inflammatory arthritis, with minimal effect on bone and cartilage. (
  • In cancer tumors, fibroblasts are triggered to respond to tissue damaged by tumors and create inflammation. (
  • however, it has remained unclear whether all their purported functions, such as inflammation, fibrosis, and damage, occur in all fibroblasts or are restricted to discrete fibroblast subsets. (
  • Subsequent deletion of FAPα-expressing fibroblasts suppressed both inflammation and bone erosions in mouse models of resolving and persistent arthritis. (
  • Adoptive transfer of FAPα + THY1 − fibroblasts into murine joints selectively mediated bone and cartilage damage with little impact on inflammation. (
  • PU.1 controls fibroblast polarization and tissue fibrosis. (
  • Pharmacological and genetic inactivation of PU.1 disrupts the fibrotic network and enables reprogramming of fibrotic fibroblasts into resting fibroblasts, leading to regression of fibrosis in several organs. (
  • Fibroblasts are therefore a key determinant in the malignant progression of cancer and represent an important target for cancer therapies. (
  • A framework for advancing our understanding of cancer-associated fibroblasts. (
  • Zhou L, Yang K, Andl T, Wickett RR, Zhang Y. Perspective of targeting cancer-associated fibroblasts in melanoma. (
  • Chini EN, Chini CCS, Espindola Netto JM, de Oliveira GC, van Schooten W. The pharmacology of CD38/NADase: an emerging target in cancer and diseases of aging. (
  • Histology of cancer-associated fibroblast (CAF) subset marker expression during PyMT tumor development. (
  • A new Tel Aviv University study published in Nature Communications on September 26 finds that fibroblasts also play a devastating role in the development of breast cancer. (
  • We have shown, for the first time, that in breast cancer these fibroblasts activate a 'misguided' wound healing response, responding to the tissue damage caused by the cancerous growth," explains Prof. Neta Erez of TAU's Sackler Faculty of Medicine, who led the research for the study. (
  • We hypothesize that cancer exosomes can alter the function of healthy fibroblast present within the tumor stroma, leading to alterations that may promote tumor growth and progression. (
  • Active fibroblasts can be recognized by their abundant rough endoplasmic reticulum. (
  • Inactive fibroblasts (called fibrocytes) are smaller, spindle-shaped, and have a reduced amount of rough endoplasmic reticulum. (
  • They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [ PMID: 7583099 ], which belong to the tyrosine kinase superfamily. (
  • Promiscuity of fibroblast growth factor receptors. (
  • Members FGF1 through FGF10 all bind fibroblast growth factor receptors (FGFRs). (
  • In our laboratory, recent single cell electrophysiologic studies have demonstrated the absence of voltage-gated Ca 2+ channels in human cardiac fibroblasts. (
  • We hypothesized that non-voltage-gated Ca 2+ -permeable TRP channels are responsible for Ca 2+ entry in human cardiac fibroblasts. (
  • Fibroblasts treated with TRPM7 siRNA for five days showed a 76.3% decrease in current density, indicating that transcription of trpm7 produces the message for the Ca 2+ -pemeable channel in human cardiac fibroblasts. (
  • Cardiac fibroblasts were treated with different concentrations (10 −8 to 10 −6 M) of Ang II for different times (6 hours, 12 hours, and 24 hours). (
  • In this study we investigated the potential role of the BRCA2 protein in cytokinesis in unmodified primary human fibroblast carrying a heterozygous mutation in the BRCA2 gene. (
  • We demonstrate that unmodified primary human fibroblasts derived from heterozygous BRCA2 mutation carriers show significantly prolonged cytokinesis. (
  • The above results demonstrate that bacterial invasion of primary cultures of fibroblasts can induce IFN production. (
  • Primary neonatal fibroblasts have been treated with mitomycin C at passage #1 and will not replicate. (
  • The autologous fibroblasts (treated and untreated) labeled with adenovirus-GFP were implanted around the wound (Φ6mm), which was created on the dorsum of each mouse. (
  • Correcting Nasojugal Groove with Autologous Cultured Fibroblast Injection: A Pilot Study. (
  • A new commercial drug that contains autologous cultured fibroblasts has been developed and approved by the United States Food and Drug Administration for improving the appearance of nasolabial folds. (
  • Differences observed between asthmatic and non-asthmatic bronchial fibroblasts (e.g., response to transforming growth factor β, cell shape, elasticity, and protein expression profile) may have a crucial influence on this phenomenon. (
  • The authors found that fibroblast activation protein-α (FAPα), a surface glycoprotein expressed by activated fibroblasts, was abundant in synovial tissues and fibroblasts isolated from patients with persistent compared to resolving RA. (
  • Protein and mRNA levels of SMAD3, but not of SMAD4 or SMAD7, were variably elevated in scleroderma fibroblasts compared with those from healthy controls. (
  • The life span of a fibroblast, as measured in chick embryos, is 57 ± 3 days. (
  • Tissue damage stimulates fibrocytes and induces the production of fibroblasts. (
  • Bacterial invasion of fibroblasts induces interferon production. (
  • The question of whether STAT3 activation is involved in fibroblast senescence remains unanswered. (
  • We aimed to characterize a model of oxidant-induced senescence in human lung fibroblasts and to determine the effect of inhibiting STAT3 activity on the development of senescence. (
  • Exposing human lung fibroblasts to 150 mu M hydrogen peroxide (H2O2) resulted in increased senescence-associated 3-galactosidase content and expression of p21 and IL-6, all of which are features of senescence. (
  • The results of this study illustrate that stress-induced senescence in lung fibroblasts involves the activation of STAT3, which can be pharmacologically modulated. (
  • This review focuses on what is known about the nature of fibroblast-to-myofibroblast transition in asthma. (
  • We aim to consider possible mechanisms and conditions that may play an important role in fibroblast-to-myofibroblast transition but have not yet been discussed in this context. (
  • Recent studies have shown that some inherent and previously undescribed features of fibroblasts can also play a significant role in fibroblast-to-myofibroblast transition. (
  • An accurate understanding and recognition of all factors affecting fibroblast-to-myofibroblast transition might provide an opportunity to discover efficient methods of counteracting this phenomenon. (
  • Fibroblast growth factors. (
  • Goldfarb M (2001) Signaling by fibroblast growth factors: the inside story. (
  • The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans. (
  • The main conclusion drawn is that these fibroblasts lose their cell identity, as if they had "forgotten" what they are, and consequently their activity is altered, thus affecting tissue. (
  • The single-cell analysis confirmed the loss of fibroblast identity in aged animals. (
  • Using sophisticated computational tools, the scientists observed that aged fibroblasts show a less defined molecular conformation compared to young fibroblasts and that"they resemble the undefined cell states observed in newborn animals," says Heyn. (
  • Pipette the cell suspension (1ml) from the vial into the T-75 flask ( SIAL0641 ) containing 15 ml of Fibroblast Growth Medium ( 116-500 ). (
  • Induced pluripotent stem cell lines derived from equine fibroblasts," Stem Cell Reviews and Reports , vol. 7, no. 3, pp. 693-702, 2011. (
  • Tissue stretch ex vivo (average 25% tissue elongation from 10 min to 2 h) caused a significant time-dependent increase in fibroblast cell body perimeter and cross-sectional area (ANOVA, P Ͻ 0.01). (
  • At 2 h, mean fibroblast cell body cross-sectional area was 201% greater in stretched than in unstretched tissue. (
  • Fibroblasts in stretched tissue had larger, ' sheetlike ' cell bodies with shorter processes. (
  • In contrast, fibroblasts in unstretched tissue had a ' dendritic ' morphology with smaller, more globular cell bodies and longer processes. (
  • The appearance of the latter, a fibroblast-like cell with abundant filopodia, enabled the sculpturing of the ECM and the formation of complex tissue-specific architectures. (
  • Mast cell basic fibroblast growth factor in silicosis. (
  • The 3T3 cell line is an important fibroblast culture, widely utilized in laboratory research, which was established from disaggregated tissue of an albino Swiss mouse ( Mus musculus ) embryo. (
  • Loosing of fibroblast cell is the main problem in aging and wrinkles and non-healed skin wounds. (
  • Biopsies from behind a patient's ear are the source of fibroblasts, which are isolated, expanded through cell culture, and used for the correction of facial contour deformities such as nasolabial folds, glabellar crease, deep wrinkles of the forehead, and acne scars. (
  • This collection includes the IMR-90 (female) and IMR-91 (male), human fetal lung fibroblast lines which were developed expressly for the NIA Aging Cell Repository and are available at low, intermediate, and high population doublings. (
  • MRC-5 (AG05965 - male) from Britain, another well characterized diploid human fetal lung fibroblast cell strain, is available at three population doubling levels. (
  • Cell surface associated glycohydrolases in normal and Gaucher disease fibroblasts. (
  • We analyzed the activities of CBE-sensitive β-glucosidase (GBA1) and AMP-DNM-sensitive β-glucosidase (GBA2) in total cell lysates and PM of human fibroblast cell lines from control (normal) subjects and from patients with GD clinical types 1, 2, and 3. (
  • Single-cell transcriptional analysis identified two distinct fibroblast subsets within the FAPα + population. (
  • For now, researchers will be able to make advances toward new clinical strategies targeting pathogenic fibroblasts by inducing phenotypic conversion, selective depletion or replacement of these important cell types via epigenetic modification, monoclonal antibody-based cell depletion, and cell-based therapies. (
  • Topical treatment with basic fibroblast growth factor promotes wound healing and barrier recovery induced by skin abrasion. (
  • By restoring fibroblasts to the burned regions, the body can restore the ECM within the wound site and recover from the injury. (
  • We hypothesized that PHD2 silenced fibroblasts would increase the expression of angiogenic factors, which might contribute to the improvement of the diabetic wound healing. (
  • Morphine at concentrations of 10(-8) to 10(-4) M promoted apoptosis of kidney fibroblasts and also enhanced the synthesis of p53 by kidney fibroblasts. (
  • Functional categorization of the differentially expressed genes identified the enrichment of genes involved in several cellular processes, including apoptosis and oxidative stress, in the fibroblasts exposed to hexavalent chromium. (
  • We provide evidence that excess activity of damage-responsive lung fibroblasts drives lethal immunopathology during severe influenza virus infection. (
  • A therapeutic agent that targets the ECM protease activity of damage-responsive lung fibroblasts could provide a promising approach to preserving lung function and improving clinical outcomes following severe respiratory infections. (
  • citation needed] Besides their commonly known role as structural components, fibroblasts play a critical role in an immune response to a tissue injury. (
  • These included FAPα + THY1 + immune effector fibroblasts located in the synovial sublining, and FAPα + THY1 - destructive fibroblasts present only in the synovial lining. (
  • Representative images show expression of the activated fibroblast marker αSMA, the developmental CAF (dCAF) marker Col9, the matrix CAF (mCAF) marker Pdgfra, the vascular CAF (vCAF) marker Rgs5, and the cycling CAF (cCAF) marker Top2a. (
  • The researchers isolated fibroblasts in transgenic mice from different stages of breast carcinogenesis and profiled the expression of all their genes. (
  • Incubation of periodontal ligament fibroblasts with bacteria or bacterial components causes an increased expression of RANKL and other osteoclastogenesis-stimulating molecules, such as tumor necrosis factor-α and macrophage-colony stimulating factor. (
  • We undertook this study to examine the expression and function of SMADs, recently characterized intracellular effectors of TGFβ signaling, in scleroderma fibroblasts. (
  • SMAD-regulated luciferase reporter expression was examined to investigate the potential functional significance of activation and nuclear accumulation of endogenous SMADs in scleroderma fibroblasts. (
  • This entry represents fibroblast growth factor 14 (FGF14), also known as fibroblast growth factor homologous factor 4. (
  • Goldfarb M (2005) Fibroblast growth factor homologous factors: evolution, structure, and function. (
  • To this end, we used the transgenic polyoma middle T oncogene-induced mouse mammary carcinoma model and performed whole transcriptome analysis in FACS-sorted fibroblasts from early- and late-stage tumors. (
  • In this study we used ex vivo and in vivo models to investigate the effect of tissue stretch on mouse subcutaneous tissue fibroblast morphology. (
  • A comparison has been made of the inhibitory and lethal effects of d -arabinosyl nucleosides and their corresponding nucleoside 5′-monophosphates on the viability of cultured mouse fibroblasts. (
  • Mouse embryo fibroblast. (
  • FGF1 is also known as acidic fibroblast growth factor , and FGF2 is also known as basic fibroblast growth factor . (
  • [13] In 1975, they further fractionated the extract using acidic and basic pH and isolated two slightly different forms that were named "acidic fibroblast growth factor" (FGF1) and "basic fibroblast growth factor" (FGF2). (
  • while FGF2, HBGF-2, and ECGF-2 were all the same basic fibroblast growth factor. (
  • More specifically, it concerns procedures for stabilizing basic fibroblast growth factor by treatment with disulfides or other compounds capable of forming S--S covalent bonds. (