Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Fibroblast Growth Factor 2: 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).Fibroblast Growth Factors: 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, Cultured: 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.Receptors, Fibroblast Growth Factor: 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.Fibroblast Growth Factor 1: 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).Skin: The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Receptor, Fibroblast Growth Factor, Type 1: 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.Receptor, Fibroblast Growth Factor, Type 2: 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).Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.RNA, Messenger: 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.Collagen: 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).3T3 Cells: 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.Receptor, Fibroblast Growth Factor, Type 3: 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.Dermis: 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.Signal Transduction: 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.Gene Expression Regulation: 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.Transfection: 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 Transformation, Neoplastic: 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.Molecular Sequence Data: 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.Keloid: 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.Fibroblast Growth Factor 10: 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.Wound Healing: Restoration of integrity to traumatized tissue.Extracellular Matrix: 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.Fibroblast Growth Factor 7: 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.Collagen Type I: 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.Growth Substances: Signal molecules that are involved in the control of cell growth and differentiation.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Chick Embryo: 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.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Actins: 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.NIH 3T3 Cells: 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 http://www.atcc.org/)Cell Aging: 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.Fibronectins: 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.Receptor, Fibroblast Growth Factor, Type 4: 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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Embryo, Mammalian: 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.Lung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.Cell Line, Transformed: 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.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.DNA: 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).Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Platelet-Derived Growth Factor: 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.Fibroblast Growth Factor 5: 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.Blotting, Western: 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.Synovial Membrane: 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.Scleroderma, Systemic: 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.Kinetics: The rate dynamics in chemical or physical systems.Fibroblast Growth Factor 4: A HEPARIN binding fibroblast growth factor that may play a role in LIMB BUDS development.Cell Adhesion: Adherence of cells to surfaces or to other cells.Cell Survival: 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.Coculture Techniques: 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.Transforming Growth Factor beta1: 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, Conditioned: 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).Recombinant Proteins: Proteins prepared by recombinant DNA technology.Mutation: 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.Reverse Transcriptase Polymerase Chain Reaction: 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.Matrix Metalloproteinase 1: 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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Amino Acid Sequence: 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.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Fluorescent Antibody Technique: 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.Mice, Knockout: 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.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Up-Regulation: 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.Cell Transformation, Viral: 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.Cell Culture Techniques: Methods for maintaining or growing CELLS in vitro.Enzyme Activation: 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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Apoptosis: 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.Connective Tissue: Tissue that supports and binds other tissues. It consists of CONNECTIVE TISSUE CELLS embedded in a large amount of EXTRACELLULAR MATRIX.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Interleukin-1: 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.Procollagen: A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal and carboxyl-terminal ends of the polypeptide chains.Pulmonary Fibrosis: 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.Cell Communication: 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.Fibroblast Growth Factor 8: 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.Stromal Cells: 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.Blotting, Northern: 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.Cell Cycle: 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.DNA-Binding Proteins: 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.Cell Transdifferentiation: 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.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Mitogens: 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)Culture Media: 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.Tumor Cells, Cultured: 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.Mice, Inbred C57BLProtein Binding: 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.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Promoter Regions, Genetic: 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.Receptors, Cell Surface: 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, Fluorescence: 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.Membrane Proteins: 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.Epidermal Growth Factor: 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.Epithelial Cells: 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.L Cells (Cell Line): A cultured line of C3H mouse FIBROBLASTS that do not adhere to one another and do not express CADHERINS.Proteins: 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.Paracrine Communication: 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.Extracellular Matrix Proteins: 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).Microbial Collagenase: 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 3.4.24.3.Molecular Weight: The sum of the weight of all the atoms in a molecule.Cell Nucleus: 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)Down-Regulation: 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.Ultraviolet Rays: 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.Mucolipidoses: 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)Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Proto-Oncogene Proteins: 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.Connective Tissue Growth Factor: 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.Keratinocytes: 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.Skin Physiological Phenomena: The functions of the skin in the human and animal body. It includes the pigmentation of the skin.Lysosomes: 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)Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Cattle: 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.Proteoglycans: Glycoproteins which have a very high polysaccharide content.Culture Media, Serum-Free: 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.Connective Tissue Cells: A group of cells that includes FIBROBLASTS, cartilage cells, ADIPOCYTES, smooth muscle cells, and bone cells.Collagenases: Enzymes that catalyze the degradation of collagen by acting on the peptide bonds.Gels: 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.Orbit: Bony cavity that holds the eyeball and its associated tissues and appendages.Intercellular Signaling Peptides and Proteins: 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.Cornea: 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)RNA, Small Interfering: 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.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.DNA Primers: 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.Glycosaminoglycans: 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.Immunoblotting: 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.Models, Biological: 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.Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.Cell Line, Tumor: A cell line derived from cultured tumor cells.Dinoprostone: 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.Cloning, Molecular: 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.Cycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.Tumor Suppressor Protein p53: 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.Myocardium: 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.Heparin: 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.Nuclear Proteins: 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.Hyaluronic Acid: 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.Diploidy: The chromosomal constitution of cells, in which each type of CHROMOSOME is represented twice. Symbol: 2N or 2X.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Mitogen-Activated Protein Kinases: 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).Tumor Necrosis Factor-alpha: 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.Avian Sarcoma Viruses: Group of alpharetroviruses (ALPHARETROVIRUS) producing sarcomata and other tumors in chickens and other fowl and also in pigeons, ducks, and RATS.Fetus: 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.Heparitin Sulfate: A heteropolysaccharide that is similar in structure to HEPARIN. It accumulates in individuals with MUCOPOLYSACCHARIDOSIS.ThymidineGenes, ras: 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.Contact Inhibition: Arrest of cell locomotion or cell division when two cells come into contact.Matrix Metalloproteinase 3: 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)Cicatrix: The fibrous tissue that replaces normal tissue during the process of WOUND HEALING.Microscopy, Electron: 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.DNA, Complementary: 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 Fusion Proteins: 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.Rabbits: 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.Flow Cytometry: 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.Bleomycin: 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.Cell Count: The number of CELLS of a specific kind, usually measured per unit volume or area of sample.Collagen Type III: 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.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.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)Polymerase Chain Reaction: 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.Oncogenes: 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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.DNA Damage: 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.Protein Biosynthesis: The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.DNA Replication: The process by which a DNA molecule is duplicated.PhosphoproteinsSmad3 Protein: 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.Gelatinases: A class of enzymes that catalyzes the degradation of gelatin by acting on the peptide bonds. EC 3.4.24.-.Retroviridae: 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).Fibroblast Growth Factor 3: A fibroblast growth factor that is expressed primarily during development.Foreskin: The double-layered skin fold that covers the GLANS PENIS, the head of the penis.Arthritis, Rheumatoid: 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.Proto-Oncogene Proteins c-sis: 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.Hybrid Cells: 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.Interleukin-6: 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.Periodontal Ligament: The fibrous CONNECTIVE TISSUE surrounding the TOOTH ROOT, separating it from and attaching it to the alveolar bone (ALVEOLAR PROCESS).Culture Techniques: 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.Vascular Endothelial Growth Factor A: 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.Mice, Inbred BALB CRats, Sprague-Dawley: 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.Cell Shape: The quality of surface form or outline of CELLS.Antibodies: 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).Swiss 3T3 Cells: A cell line established in 1962 from disaggregated Swiss albino mouse embryos. This fibroblast cell line is extremely popular in research.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Cytokines: 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.Simian virus 40: A species of POLYOMAVIRUS originally isolated from Rhesus monkey kidney tissue. It produces malignancy in human and newborn hamster kidney cell cultures.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Neovascularization, Physiologic: The development of new BLOOD VESSELS during the restoration of BLOOD CIRCULATION during the healing process.Mitogen-Activated Protein Kinase 3: 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.Genes, src: 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.Precipitin Tests: 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.Matrix Metalloproteinase 2: A secreted endopeptidase homologous with INTERSTITIAL COLLAGENASE, but which possesses an additional fibronectin-like domain.Granulation Tissue: 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.

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.
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 ...
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 ...
... 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.
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] www.premierlab.com 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 ...
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 ...
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 - Expression profiles of p53-, p16INK4a-, and telomere-regulating genes in replicative senescent primary human, mouse, and chicken fibroblast cells. AU - Kim, Hyunggee. AU - You, Seungkwon. AU - Farris, James. AU - Kong, Byung Whi. AU - Christman, Shelly A.. AU - Foster, Linda K.. AU - Foster, Douglas N.. PY - 2002/9/2. Y1 - 2002/9/2. N2 - Replicative senescence is known to be an intrinsic mechanism in determining the finite life span of in vitro cultured cells. Since this process is recognized as an evolutionarily conserved mechanism from yeast to mammalian cells, we compared the senescence-associated genetic alterations in the p53, p16INK4a, and telomere regulatory pathways using replicative senescent human, mouse, and chicken fibroblast cells. Normal human diploid fibroblast (HDF; WI38) and chicken embryonic fibroblast (CEF) cells were shown to have a more extended in vitro proliferative potential than their mouse embryonic fibroblast (MEF) counterpart. In contrast to the HDF ...
Human Cardiac Fibroblast cDNA https://www.sciencepro.com.br/produtos/sc-6304 https://www.sciencepro.com.br/@@site-logo/logo-novo.png ...
אנו מתארים הליך ניסוי פשוט ומהיר ליצירת fibroblasts העיקרי מהאוזניים והזנבות של עכברים. ההליך...
Cancer-associated fibroblasts (CAFs) are one of the key determinants in the malignant progression of cancer. The subject of this research was metabolic reorganization of CAFs and their participation in collagen cross-linking process. The metabolic differences between normal fibroblasts and CAFs were elucidated using two-photon fluorescence lifetime imaging microscopy (FLIM). Collagen structure in 3D model was assessed using second harmonic generation (SHG) microscopy. We show increased metabolic activity of fibroblasts derived from patients colon tumor with a shift to more oxidative metabolism compare to dermal fibroblasts. The results of the study of collagen suggest that CAFs may contribute to the tumor progression through the facilitation of collagen alignment. In general, our findings support the idea of the strong association between cancer cells and fibroblasts and extensive involvement of CAFs in modulation of tumor microenvironment ...
Draye, JP. ; Quintart, J. ; Courtoy, Pierre J. ; Baudhuin, Pierre. Fate of I-125-labeled Plasma-membrane Polypeptides in Cultured Rat Fibroblasts - Quantification of Their Association With Lysosomes.In: Archives Internationales de Physiologie et de Biochimie, Vol. 92, no. 5, p. B131-B132 (1984 ...
SuperCult® Fibroblast Growth Medium Kit-CD is a serum-free, chemically defined medium for the growth of adult and neonatal human Dermal Fibroblast Cells. SuperCult® Fibroblast Growth Medium Kit-CD is optimized for multiple passage expansion of NHDFs. Cells can be directly transitioned from serum-containing medium to SuperCult® Fibroblast Growth Medium Kit-CD with little to no adaptation time. In addition, dermal fibroblasts grow on any culture ware and need no attachment matrix before adding SuperCult® Fibroblast Growth Medium Kit-CD ...
P. S. RUDLAND, A. E. SMITH, S. WEIL; Translational Control of Protein Synthesis after Re-initiation of the Growth of Cultured Mouse Fibroblasts. Biochem Soc Trans 1 December 1975; 3 (6): 1145-1148. doi: https://doi.org/10.1042/bst0031145. Download citation file:. ...
Objective. Synovial fibroblasts share a number of phenotype markers with fibroblasts derived from bone marrow. In this study we investigated the role of matched fibroblasts obtained from 3 different sources (bone marrow, synovium, and skin) to test the hypothesis that synovial fibroblasts share similarities with bone marrow-derived fibroblasts in terms of their ability to support survival of T cells and neutrophils. Methods. Matched synovial, bone marrow, and skin fibroblasts were established from 8 different patients with rheumatoid arthritis who were undergoing knee or hip surgery. Resting or activated fibroblasts were cocultured with either CD4 T cells or neutrophils, and the degree of leukocyte survival, apoptosis, and proliferation were measured. Results. Fibroblasts derived from all 3 sites supported increased survival of CD4 T cells, mediated principally by interferon-beta. However, synovial and bone marrow fibroblasts shared an enhanced site-specific ability to maintain CD4 T cell ...
Results 1. The proliferation of CFb is significantly promoted after adding Ang II, compared with the control group (p,0.05 or p,0.01). The 100 μg/l TP showed the effect of inhibiting the proliferation of CFb at the first 24 h (p,0.01), reached a peak within 48 h (p,0.001), started to diminish after 72 h, indicate the best time to exert effects were at 2 to 3 days. 2. With the time increase after adding Ang II, collagen synthesis increased, there is significant difference compared with the control group (p,0.05 or p,0.01). After 24 h, 48 h, 72 h of adding TP, the collagen content of each group compared with the Ang II group were significantly different. The effect of high concentration TP (100 μg/l) reached the peak (p,0.001) at 48 h (p,0.001). 3. After 24 h of adding Ang II, TGF-β1 expression was significantly increased (p,0.01). After 24 h of adding different concentrations of TP, TGF-β1 expression were significantly decreased (p,0.05 or p,0.01). 4. After 30min of adding Ang II, ERK1/2 ...
Cancer-associated fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation, and invasion. We demonstrate that CAFs also mediate tumor-enhancing inflammation. Using a mouse model of squamous skin carcinogenesis, we found a proinflammatory gene signature in CAFs isolated from dysplastic skin. This signature was maintained in CAFs from subsequent skin carcinomas and was evident in mammary and pancreatic tumors in mice and in cognate human cancers. The inflammatory signature was already activated in CAFs isolated from the initial hyperplastic stage in multistep skin tumorigenesis. CAFs from this pathway promoted macrophage recruitment, neovascularization, and tumor growth, activities that are abolished when NF-kappaB signaling was inhibited. Additionally, we show that normal dermal fibroblasts can be educated by carcinoma cells to express proinflammatory genes.
Inhibitors of fibroblast proliferation Invasins Chemotactic inhibitors Collagenase Bacteriocins Immunosuppressive proteins Bone ...
PDGF[1][2] is a potent mitogen for cells of mesenchymal origin, including fibroblasts, smooth muscle cells and glial cells. In ... PDGF is a required element in cellular division for fibroblasts, a type of connective tissue cell that is especially prevalent ... It has also been shown that fibroblast growth factor (FGF) activates a signaling pathway that positively regulates the PDGF ... of mesenchymal cells such as fibroblasts, osteoblasts, tenocytes, vascular smooth muscle cells and mesenchymal stem cells as ...
Fibroblast. .mw-parser-output .nobold{font-weight:normal}. FGF receptor ligands:. *FGF1/FGF2/FGF5 ...
Fibroblast growth factor 20 is a protein which in humans is encoded by the FGF20 gene.[1] ... The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad ...
Fibroblast. .mw-parser-output .nobold{font-weight:normal}. FGF receptor ligands:. *FGF1/FGF2/FGF5 ...
KGF is a small signaling molecule that binds to fibroblast growth factor receptor 2b (FGFR2b).[1] For signalling to occur, a ...
Fibroblast. .mw-parser-output .nobold{font-weight:normal}. FGF receptor ligands:. *FGF1/FGF2/FGF5 ...
Fibroblast growth. ↑Apoptosis Antithrombotic ↓Thromboxane-A2. ↓PDGF ↓Platelet aggregation. ↓Platelet adherence to vessel wall ...
Fibroblasts are the most common cell type in connective tissue ECM, in which they synthesize, maintain, and provide a ... Elastins are synthesized by fibroblasts and smooth muscle cells. Elastins are highly insoluble, and tropoelastins are secreted ... Hadjipanayi E, Mudera V, Brown RA (February 2009). "Close dependence of fibroblast proliferation on collagen scaffold matrix ... "Mechanoregulation of gene expression in fibroblasts". Gene. 391 (1-2): 1-15. doi:10.1016/j.gene.2007.01.014. PMC 2893340. PMID ...
Colony-forming unit-fibroblast (CFU-F). *Mesenchymal stem cell / marrow stromal cell (MSC) ...
... has been shown to inhibit TGF-beta-mediated conversion of pulmonary fibroblasts into myofibroblasts in COPD and ... "Anti-fibrotic effects of theophylline on lung fibroblasts". Biochemical and Biophysical Research Communications. 341 (3): 684- ...
Phosphorylation of H2AX at short telomeres in T cells and fibroblasts. „J Biol Chem". 279 (43), s. 45148-54, Oct 2004. DOI: ... Telomeres shorten during ageing of human fibroblasts.. „Nature". 345 (6274), s. 458-60, May 1990. DOI: 10.1038/345458a0. PMID: ... Telomeres shorten during ageing of human fibroblasts. „Nature". 345 (6274), s. 458-60, May 1990. DOI: 10.1038/345458a0. PMID: ...
1992). "Telomere length predicts replicative capacity of human fibroblasts". Proc. Natl. Acad. Sci. U.S.A. 89: 10114-10118. ...
"Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts". Science. 275 (5306): 1649-52. doi:10.1126/science. ...
2007). "Islet-derived fibroblast-like cells are not derived via epithelial-mesenchymal transition from Pdx-1 or insulin- ... Twist1 and Twist2, as well as ZEB1 protects human cells and mouse embryonic fibroblasts from senescence. Similarly, TGF-β can ... Kepner, N.; Lipton, A. (February 1981). "A mitogenic factor for transformed fibroblasts from human platelets". Cancer Research ... which is to be synthesized by fibroblasts and osteoblasts that encircle the neural tube. The major source of these cells are ...
Quaglino, Daniela; Boraldi, Federica; Bini, Luca; Volpi, Nicola (April 2004). "The Protein Profile of Fibroblasts: The Role of ...
An interphase female human fibroblast cell.[1] Arrows point to sex chromatin on DNA (DAPI) in cell nucleus(left), and to the ... The figure shows confocal microscopy images from a combined RNA-DNA FISH experiment for Xist in fibroblast cells from adult ...
Fibroblasts also secrete growth factors that attract epithelial cells to the wound site. Hypoxia also contributes to fibroblast ... Simultaneously with angiogenesis, fibroblasts begin accumulating in the wound site. Fibroblasts begin entering the wound site ... macrophage and mast cells release fibroblast growth and chemotactic factors to activate fibroblasts from adjacent tissue. ... Fibroblasts lay down collagen to reinforce the wound as myofibroblasts contract.[3] The contraction stage in proliferation ends ...
Stimulation of the fibroblast, in particular, seems to be crucial to the disease process, and studies have converged on the ... and the fibroblast (possibly in response to other stimuli) also overexpresses the receptor for this mediator. An intracellular ... and this too seems to be due to collagen accumulation by fibroblasts, although direct alterations by cytokines, platelet ...
The mouse embryonic fibroblasts were reprogrammed into thymic epithelial cells (TECs) by enforcing the expression of one ... A fully functional thymus derived from reprogrammed mouse embryonic fibroblasts has been grown in the kidney capsule of mice. ... "An organized and functional thymus generated from FOXN1-reprogrammed fibroblasts". Nature Cell Biology. 16 (9): 902-908. doi: ...
Katz Y, Strunk RC (March 1989). "Synthesis and regulation of C1 inhibitor in human skin fibroblasts". Journal of Immunology. ...
Salk, D; Au, K; Hoehn, H; Martin, GM (1981). "Cytogenetics of Werner's syndrome cultured skin fibroblasts: Variegated ... "Blocking protein farnesyltransferase improves nuclear shape in fibroblasts from humans with progeroid syndromes". Proceedings ...
In a series of sequential experiments, Weintraub and his students showed that myoD was able to convert fibroblasts (connective ... Groudine, M; Weintraub, H (1975). "Rous sarcoma virus activates embryonic globin genes in chick fibroblasts". Proc Natl Acad ... "Transfection of a DNA locus that mediates the conversion of 10T1/2 fibroblasts to myoblasts". Cell. 47 (5): 649-656. doi: ... a nuclear phosphoprotein requiring a Myc homology region to convert fibroblasts to myoblasts". Science. 242 (4877): 405-411. ...
"Mitochondrial bioenergetics and dynamics interplay in complex I-deficient fibroblasts". Biochimica et Biophysica Acta. 1802 (5 ...
The further roteins increase the vascular fluid, fibroblasts and promote the ploriferation of mast cells which produce the ... this will increase the production of fibroblasts and mast cells. Lymphatic obstruction due to any cause can increase the amount ...
Similar results are observed after the application of mechanical loading to these fibroblasts. Periodontal ligament fibroblasts ... Periodontal ligament fibroblasts have the capacity to select and attract osteoclast precursors and subsequently to retract and ... Periodontal ligament fibroblasts produce primarily OPG, an osteoclastogenesis-inhibitory molecule. However, they may be ... During the last decade it has become clear that periodontal ligament fibroblasts may contribute to the in vitro differentiation ...
The CM-chitosan could reduce the ratio of type I/III collagen in keloid fibroblast by inhibiting the secretion of collagen type ... The CM-chitosan could reduce the ratio of type I/III collagen in keloid fibroblast by inhibiting the secretion of collagen type ... The CM-chitosan could reduce the ratio of type I/III collagen in keloid fibroblast by inhibiting the secretion of collagen type ... The CM-chitosan could reduce the ratio of type I/III collagen in keloid fibroblast by inhibiting the secretion of collagen type ...
Fibroblast growth factors play crucial roles in angiogenesis and are involved in the proliferation and differentiation of ... Recombinant Human Acidic Fibroblast Growth Factor, rHu aFGF. Log in for price ...
We describe the effects of IL-13 on collagen homeostasis from normal (NF) and keloid (KF) fibroblasts and compare these effects ... We describe the effects of IL-13 on collagen homeostasis from normal (NF) and keloid (KF) fibroblasts and compare these effects ... We describe the effects of IL-13 on collagen homeostasis from normal (NF) and keloid (KF) fibroblasts and compare these effects ... We describe the effects of IL-13 on collagen homeostasis from normal (NF) and keloid (KF) fibroblasts and compare these effects ...
TGF-β1 and collagen in keloid fibroblast and normal skin fibroblast. Fibroblasts were cultured by applying explant method to ... The levels of LTB4, TGF-β1, collagen 1 and collagen 3 increase in keloid fibroblast. Such a result shows the role of LTB4 in ... The level of collagen 1 is higher than that of collagen 3 in keloid fibroblast. Leukotriene B4 (LTB4) is one of the derivative ... The levels of LTB4, TGF-β1 are higher in keloid fibroblast, despite the fact that it does not show statistically significant ...
Acidic fibroblast growth factor gene 5′ non‐coding exon and flanking region from hamster DDT1 cells: Identification of the ... Acidic fibroblast growth factor gene 5′ non‐coding exon and flanking region from hamster DDT1 cells: Identification of the ... Acidic fibroblast growth factor gene 5′ non‐coding exon and flanking region from hamster DDT1 cells : Identification of the ... title = "Acidic fibroblast growth factor gene 5′ non‐coding exon and flanking region from hamster DDT1 cells: Identification of ...
Crystal structure of L44F/F132W mutant of Human acidic fibroblast growth factor ... Crystal structure of L44F/F132W mutant of Human acidic fibroblast growth factor; X-RAY DIFFRACTION 1.90 Å SMTL ID. 3fjd.1. ...
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 ...
... Stephen Knight stigh at med.unc.edu 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 zmk.unibe.ch Fibroblasts should not be difficult to culture on microcarrier ...
... poulain at itsa.ucsf.edu poulain at itsa.ucsf.edu 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 ...
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, ...
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.. ...
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. ...
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 ...
... Asta Björk Jonsdottir,1,2,3 Maaike P. G. Vreeswijk,4 Ron ... In this study we investigated the potential role of the BRCA2 protein in cytokinesis in unmodified primary human fibroblast ... Results: We demonstrate that unmodified primary human fibroblasts derived from heterozygous BRCA2 mutation carriers show ...
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 ...
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 ...
  • 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). (news-medical.net)
  • Stiffening of human skin fibroblasts with. (mendeley.com)
  • 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. (nih.gov)
  • IMR-91 diploid male fetal skin fibroblasts cultures are also available at low, intermediate, and high population doublings. (coriell.org)
  • 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? (sclero.org)
  • 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. (protocol-online.org)
  • 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). (doaj.org)
  • Fibroblasts help to create connective tissue that supports, anchors and connects various parts of the body. (smore.com)
  • 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. (mendeley.com)
  • 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. (wikipedia.org)
  • 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. (medscape.com)
  • 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 ]. (ebi.ac.uk)
  • Fibroblast growth factors (FGFs) and their receptors (FGF receptors) constitute a signalling system conserved throughout animal evolution. (els.net)
  • The fibroblast growth factors (FGFs) form a large family of structurally related, multifunctional proteins that regulate various biological responses 1 . (nature.com)
  • Affinity for fibroblast growth factors (FGFs) is increased by heparan sulfate glycosaminoglycans that function as coreceptors. (rcsb.org)
  • 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. (innovations-report.com)
  • 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. (innovations-report.com)
  • 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. (springer.com)
  • 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. (ebi.ac.uk)
  • The heparin-binding (fibroblast) growth factor family of proteins. (ebi.ac.uk)
  • 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. (wikipedia.org)
  • A mitogenic growth factor activity was found in pituitary extracts by Armelin in 1973 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. (wikipedia.org)
  • 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. (wikipedia.org)
  • Cyclic mechanical loading reduced the mRNA expression of the myofibroblast marker α-smooth muscle actin and the extracellular matrix proteins type-I, type-III, and type-V collagen, and tenascin C. These outcomes indicate that fibroblast-to-myofibroblast differentiation is reduced. (uva.nl)
  • 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. (diva-portal.org)
  • While fibroblasts are collectively known to produce collagen and other proteins in skin and connective tissues, new data points to functional variances amongst sub-groups of fibroblasts-and one in particular with a major collagen-building role when it comes to wound healing . (skininc.com)
  • 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. (aacrjournals.org)
  • were surprised to see that normal fibroblasts retained many mesenchymal characteristics when Snail1 was removed. (innovations-report.com)
  • 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. (nih.gov)
  • 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. (alzforum.org)
  • We identified five transcription factors that reprogram mouse and human fibroblasts into noxious stimulus-detecting (nociceptor) neurons. (broadinstitute.org)
  • 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' ). (nanowerk.com)
  • 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. (protocol-online.org)
  • 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. (ahajournals.org)
  • Ang II-mediated oxidative stress could be important in enhanced fibroblast growth and collagen formation. (ahajournals.org)
  • 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. (ahajournals.org)
  • Thus, pioglitazone attenuates Ang II-mediated collagen type I synthesis in cardiac fibroblasts. (ahajournals.org)
  • 3,4 Fibroblasts are the major source of collagen in the myocardium. (ahajournals.org)
  • This particular sub-group of fibroblasts, referred to as CD26+, expressed relatively high levels of type I collagen, a hallmark of fibroblasts. (skininc.com)
  • Furthermore, the researchers noted the proportion of CD26+ fibroblasts in young versus aged skin is similar, indicating the loss of collagen production during aging does not involve a reduction in CD26+ fibroblasts. (skininc.com)
  • 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. (wikipedia.org)
  • However, the role of fibroblasts in mediating inflammation is not well understood. (news-medical.net)
  • Functionally distinct fibroblast subsets mediate inflammation or tissue damage in inflammatory arthritis. (sciencemag.org)
  • 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. (sciencemag.org)
  • Subsequent deletion of FAPα-expressing fibroblasts suppressed both inflammation and bone erosions in mouse models of resolving and persistent arthritis. (sciencemag.org)
  • Adoptive transfer of FAPα + THY1 − fibroblasts into murine joints selectively mediated bone and cartilage damage with little impact on inflammation. (sciencemag.org)
  • 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). (mendeley.com)
  • A transcription factor known to drive the formation of fibroblasts during development also promotes their ability to invade and remodel surrounding tissues, report Rowe et al. (innovations-report.com)
  • A detailed protocol for preparation of human fibroblasts from scar tissues is also provided. (springer.com)
  • 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. (sciencemag.org)
  • 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. (rug.nl)
  • 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. (rug.nl)
  • The present study investigated the role of phosphatidylinositol-3-kinase (PI3K)/Akt in fibrogenesis of human lung fibroblasts and its regulation by reactive oxygen species (ROS). (cdc.gov)
  • We have shown that this transient treatment leads to persistent changes in cardiac fibroblast physiology that improves inflammatory and fibrotic responses to injury. (news-medical.net)
  • Taken together, our results indicate that TRPM7 provides the molecular basis of the Ca 2+ -permeable cation channel in human cardiac fibroblast, and that TRPM7 may play a crucial role in the fibrogenesis cascade in human heart. (ahajournals.org)
  • Active fibroblasts can be recognized by their abundant rough endoplasmic reticulum. (wikipedia.org)
  • 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. (news-medical.net)
  • The single-cell analysis confirmed the loss of fibroblast identity in aged animals. (news-medical.net)
  • 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. (news-medical.net)
  • Pipette the cell suspension (1ml) from the vial into the T-75 flask ( SIAL0641 ) containing 15 ml of Fibroblast Growth Medium ( 116-500 ). (sigmaaldrich.com)
  • Induced pluripotent stem cell lines derived from equine fibroblasts," Stem Cell Reviews and Reports , vol. 7, no. 3, pp. 693-702, 2011. (hindawi.com)
  • At 2 h, mean fibroblast cell body cross-sectional area was 201% greater in stretched than in unstretched tissue. (mendeley.com)
  • Fibroblasts in stretched tissue had larger, ' sheetlike ' cell bodies with shorter processes. (mendeley.com)
  • In contrast, fibroblasts in unstretched tissue had a ' dendritic ' morphology with smaller, more globular cell bodies and longer processes. (mendeley.com)
  • 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. (jhu.edu)
  • 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. (microscopyu.com)
  • In our laboratory, recent single cell electrophysiologic studies have demonstrated the absence of voltage-gated Ca 2+ channels in human cardiac fibroblasts. (ahajournals.org)
  • Loosing of fibroblast cell is the main problem in aging and wrinkles and non-healed skin wounds. (bioportfolio.com)
  • 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. (bioportfolio.com)
  • 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. (coriell.org)
  • MRC-5 (AG05965 - male) from Britain, another well characterized diploid human fetal lung fibroblast cell strain, is available at three population doubling levels. (coriell.org)
  • Cell surface associated glycohydrolases in normal and Gaucher disease fibroblasts. (biomedsearch.com)
  • 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. (biomedsearch.com)
  • Single-cell transcriptional analysis identified two distinct fibroblast subsets within the FAPα + population. (sciencemag.org)
  • 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. (sciencemag.org)
  • The study, published in the Journal of Investigative Dermatology , explained how using flow cytometry and immunohistology, CD26, in combination with the cell surface glycoprotein CD90, successfully identified a subpopulation of fibroblasts. (skininc.com)
  • Conclusions These results indicate that endogenous cardiac fibroblasts can be a cell source for new cardiomyocytes and that direct cardiac reprogramming can be induced in vivo by local delivery of GMT into the infarct heart. (ahajournals.org)
  • The present report deals with a series of experiments on the effects of cystamine, cysteamine and cysteine when added to cultures of chick fibroblasts shortly before irradiation. (nature.com)
  • The above results demonstrate that bacterial invasion of primary cultures of fibroblasts can induce IFN production. (jimmunol.org)
  • The F1F0-ATPase activity of mitochondrial complex V can be rapidly measured in sonicated preparations of monolayer skin fibroblast cultures from children. (biomedsearch.com)
  • 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. (nih.gov)
  • We hypothesized that PHD2 silenced fibroblasts would increase the expression of angiogenic factors, which might contribute to the improvement of the diabetic wound healing. (plos.org)
  • 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. (uva.nl)
  • We undertook this study to examine the expression and function of SMADs, recently characterized intracellular effectors of TGFβ signaling, in scleroderma fibroblasts. (wiley.com)
  • SMAD-regulated luciferase reporter expression was examined to investigate the potential functional significance of activation and nuclear accumulation of endogenous SMADs in scleroderma fibroblasts. (wiley.com)