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.Immediate-Early Proteins: Proteins that are coded by immediate-early genes, in the absence of de novo protein synthesis. The term was originally used exclusively for viral regulatory proteins that were synthesized just after viral integration into the host cell. It is also used to describe cellular proteins which are synthesized immediately after the resting cell is stimulated by extracellular signals.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.Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Connective Tissue: Tissue that supports and binds other tissues. It consists of CONNECTIVE TISSUE CELLS embedded in a large amount of EXTRACELLULAR MATRIX.Nephroblastoma Overexpressed Protein: A CCN protein family member found at high levels in NEPHROBLASTOMA cells. It is found both intracellularly and in the EXTRACELLULAR MATRIX and may play a role in the regulation of CELL PROLIFERATION and EXTRACELLULAR MATRIX synthesis.Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.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.Growth Substances: Signal molecules that are involved in the control of cell growth and differentiation.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Connective Tissue Diseases: A heterogeneous group of disorders, some hereditary, others acquired, characterized by abnormal structure or function of one or more of the elements of connective tissue, i.e., collagen, elastin, or the mucopolysaccharides.Cysteine-Rich Protein 61: A CCN protein family member that regulates a variety of extracellular functions including CELL ADHESION; CELL MIGRATION; and EXTRACELLULAR MATRIX synthesis. It may play an important role in the development of branched CAPILLARIES during EMBRYOGENESIS.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.Connective Tissue Cells: A group of cells that includes FIBROBLASTS, cartilage cells, ADIPOCYTES, smooth muscle cells, and bone cells.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.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.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.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).CCN Intercellular Signaling Proteins: A family of secreted proteins found associated with the EXTRACELLULAR MATRIX and cell surface receptors. They are believed to play a role in modulating the effects of a variety of GROWTH FACTORS and PROTEASES at the cell membrane extracellular matrix. The CCN protein family is named after three protypical members; CYSTEINE-RICH PROTEIN 61; CONNECTIVE TISSUE GROWTH FACTOR; and NEPHROBLASTOMA OVEREXPRESSED PROTEIN.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.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.Skin: The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.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.Myofibroblasts: Spindle-shaped cells with characteristic CONTRACTILE PROTEINS and structures that contribute to the WOUND HEALING process. They occur in GRANULATION TISSUE and also in pathological processes such as FIBROSIS.Cystic Fibrosis: An autosomal recessive genetic disease of the EXOCRINE GLANDS. It is caused by mutations in the gene encoding the CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR expressed in several organs including the LUNG, the PANCREAS, the BILIARY SYSTEM, and the SWEAT GLANDS. Cystic fibrosis is characterized by epithelial secretory dysfunction associated with ductal obstruction resulting in AIRWAY OBSTRUCTION; chronic RESPIRATORY INFECTIONS; PANCREATIC INSUFFICIENCY; maldigestion; salt depletion; and HEAT PROSTRATION.Smad Proteins: A family of proteins that are involved in the translocation of signals from TGF-BETA RECEPTORS; BONE MORPHOGENETIC PROTEIN RECEPTORS; and other surface receptors to the CELL NUCLEUS. They were originally identified as a class of proteins that are related to the mothers against decapentaplegic protein, Drosophila and sma proteins from CAENORHABDITIS ELEGANS.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.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.Smad3 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.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Mixed Connective Tissue Disease: A syndrome with overlapping clinical features of systemic lupus erythematosus, scleroderma, polymyositis, and Raynaud's phenomenon. The disease is differentially characterized by high serum titers of antibodies to ribonuclease-sensitive extractable (saline soluble) nuclear antigen and a "speckled" epidermal nuclear staining pattern on direct immunofluorescence.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.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.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.Smad2 Protein: A receptor-regulated smad protein that undergoes PHOSPHORYLATION by ACTIVIN RECEPTORS, TYPE I. It regulates TRANSFORMING GROWTH FACTOR BETA and ACTIVIN signaling.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.Corneal Keratocytes: Fibroblasts which occur in the CORNEAL STROMA.Wound Healing: Restoration of integrity to traumatized tissue.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.Houttuynia: A plant genus of the family SAURURACEAE. Members contain aristolactams.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.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.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).Mesangial Cells: Smooth muscle-like cells adhering to the wall of the small blood vessels of the KIDNEY at the glomerulus and along the vascular pole of the glomerulus in the JUXTAGLOMERULAR APPARATUS. They are myofibroblasts with contractile and phagocytic properties. These cells and their MESANGIAL EXTRACELLULAR MATRIX constitute the GLOMERULAR MESANGIUM.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.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.Transforming Growth Factor beta2: A TGF-beta subtype that was originally identified as a GLIOBLASTOMA-derived factor which inhibits the antigen-dependent growth of both helper and CYTOTOXIC T LYMPHOCYTES. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta2 and TGF-beta2 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor.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.Nephritis, Interstitial: Inflammation of the interstitial tissue of the kidney. This term is generally used for primary inflammation of KIDNEY TUBULES and/or surrounding interstitium. For primary inflammation of glomerular interstitium, see GLOMERULONEPHRITIS. Infiltration of the inflammatory cells into the interstitial compartment results in EDEMA, increased spaces between the tubules, and tubular renal dysfunction.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.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.Ureteral Obstruction: Blockage in any part of the URETER causing obstruction of urine flow from the kidney to the URINARY BLADDER. The obstruction may be congenital, acquired, unilateral, bilateral, complete, partial, acute, or chronic. Depending on the degree and duration of the obstruction, clinical features vary greatly such as HYDRONEPHROSIS and obstructive nephropathy.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Glomerular Mesangium: The thin membranous structure supporting the adjoining glomerular capillaries. It is composed of GLOMERULAR MESANGIAL CELLS and their EXTRACELLULAR MATRIX.Receptors, Transforming Growth Factor beta: Cell-surface proteins that bind transforming growth factor beta and trigger changes influencing the behavior of cells. Two types of transforming growth factor receptors have been recognized. They differ in affinity for different members of the transforming growth factor beta family and in cellular mechanisms of action.Mice, Inbred C57BLEpithelial 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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.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)Hepatic Stellate Cells: Perisinusoidal cells of the liver, located in the space of Disse between HEPATOCYTES and sinusoidal endothelial cells.Zanthoxylum: A plant genus of the family RUTACEAE. Some members of Zanthoxylum are reclassified from ELEUTHEROCOCCUS, Melicope, and EVODIA. The twigs are used as dental brushing sticks (TOOTHBRUSHING). Most plants that are called Fagara have been reclassified as Zanthoxylum, however some Fagara were reclassified to MELICOPE (also in the Rutacea family) or to GLEDITSIA (a genus in the FABACEAE family).Rats, 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.Receptor, Epidermal Growth Factor: A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.Lung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.Insulin-Like Growth Factor Binding Proteins: A family of soluble proteins that bind insulin-like growth factors and modulate their biological actions at the cellular level. (Int J Gynaecol Obstet 1992;39(1):3-9)Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Collagen Type IV: A non-fibrillar collagen found in the structure of BASEMENT MEMBRANE. Collagen type IV molecules assemble to form a sheet-like network which is involved in maintaining the structural integrity of basement membranes. The predominant form of the protein is comprised of two alpha1(IV) subunits and one alpha2(IV) subunit, however, at least six different alpha subunits can be incorporated into the heterotrimer.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.Diabetic Nephropathies: KIDNEY injuries associated with diabetes mellitus and affecting KIDNEY GLOMERULUS; ARTERIOLES; KIDNEY TUBULES; and the interstitium. Clinical signs include persistent PROTEINURIA, from microalbuminuria progressing to ALBUMINURIA of greater than 300 mg/24 h, leading to reduced GLOMERULAR FILTRATION RATE and END-STAGE RENAL DISEASE.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Diabetes Mellitus, Experimental: Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY.In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Focal Epithelial Hyperplasia: Hyperplasia of the mucous membrane of the lips, tongue, and less commonly, the buccal mucosa, floor of the mouth, and palate, presenting soft, painless, round to oval sessile papules about 1 to 4 mm in diameter. The condition usually occurs in children and young adults and has familial predilection, lasting for several months, sometimes years, before running its course. A viral etiology is suspected, the isolated organism being usually the human papillomavirus. (Jablonski, Illustrated Dictionary of Dentistry; Belshe, Textbook of Human Virology, 2d ed, p954)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).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.Kidney Diseases: Pathological processes of the KIDNEY or its component tissues.Fibromatosis, Gingival: Generalized or localized diffuse fibrous overgrowth of the gingival tissue, usually transmitted as an autosomal dominant trait, but some cases are idiopathic and others produced by drugs. The enlarged gingiva is pink, firm, and has a leather-like consistency with a minutely pebbled surface and in severe cases the teeth are almost completely covered and the enlargement projects into the oral vestibule. (Dorland, 28th ed)Kidney Tubules: Long convoluted tubules in the nephrons. They collect filtrate from blood passing through the KIDNEY GLOMERULUS and process this filtrate into URINE. Each renal tubule consists of a BOWMAN CAPSULE; PROXIMAL KIDNEY TUBULE; LOOP OF HENLE; DISTAL KIDNEY TUBULE; and KIDNEY COLLECTING DUCT leading to the central cavity of the kidney (KIDNEY PELVIS) that connects to the URETER.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Polygeline: A 3.5 per cent colloidal solution containing urea-cross-linked polymerized peptides. It has a molecular weight of approximately 35,000 and is prepared from gelatin and electrolytes. The polymeric solution is used as a plasma expander.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.Hepatocyte Growth Factor: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is PROTO-ONCOGENE PROTEINS C-MET.Insulin-Like Growth Factor I: A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.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.Amino Acids, DicarboxylicBlotting, 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.rhoA GTP-Binding Protein: A RHO GTP-BINDING PROTEIN involved in regulating signal transduction pathways that control assembly of focal adhesions and actin stress fibers. This enzyme was formerly listed as EC 3.6.1.47.Chondrocytes: Polymorphic cells that form cartilage.Pericytes: Unique slender cells with multiple processes extending along the capillary vessel axis and encircling the vascular wall, also called mural cells. Pericytes are imbedded in the BASEMENT MEMBRANE shared with the ENDOTHELIAL CELLS of the vessel. Pericytes are important in maintaining vessel integrity, angiogenesis, and vascular remodeling.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).Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Transforming Growth Factors: Hormonally active polypeptides that can induce the transformed phenotype when added to normal, non-transformed cells. They have been found in culture fluids from retrovirally transformed cells and in tumor-derived cells as well as in non-neoplastic sources. Their transforming activities are due to the simultaneous action of two otherwise unrelated factors, TRANSFORMING GROWTH FACTOR ALPHA and TRANSFORMING GROWTH FACTOR BETA.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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.MAP Kinase Signaling System: An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.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.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Oligonucleotides, Antisense: Short fragments of DNA or RNA that are used to alter the function of target RNAs or DNAs to which they hybridize.Neovascularization, Physiologic: The development of new BLOOD VESSELS during the restoration of BLOOD CIRCULATION during the healing process.Lysophospholipids: Derivatives of PHOSPHATIDIC ACIDS that lack one of its fatty acyl chains due to its hydrolytic removal.Proteoglycans: Glycoproteins which have a very high polysaccharide content.Cicatrix: The fibrous tissue that replaces normal tissue during the process of WOUND HEALING.Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ASCORBIC ACID can result in impaired hydroxyproline formation.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.Angiotensin II: An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.Trabecular Meshwork: A porelike structure surrounding the entire circumference of the anterior chamber through which aqueous humor circulates to the canal of Schlemm.Alkadienes: Acyclic branched or unbranched hydrocarbons having two carbon-carbon double bonds.Filtering Surgery: A surgical procedure used in treatment of glaucoma in which an opening is created through which aqueous fluid may pass from the anterior chamber into a sac created beneath the conjunctiva, thus lowering the pressure within the eye. (Hoffman, Pocket Glossary of Ophthalmologic Terminology, 1989)Cell Adhesion: Adherence of cells to surfaces or to other cells.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.Thrombospondin 1: An extracellular matrix glycoprotein from platelets and a variety of normal and transformed cells of both mesenchymal and epithelial origin. Thrombospondin-1 is believed to play a role in cell migration and proliferation, during embryogenesis and wound repair. Also, it has been studied for its use as a potential regulator of tumor growth and metastasis.Endothelial Growth Factors: These growth factors are soluble mitogens secreted by a variety of organs. The factors are a mixture of two single chain polypeptides which have affinity to heparin. Their molecular weight are organ and species dependent. They have mitogenic and chemotactic effects and can stimulate endothelial cells to grow and synthesize DNA. The factors are related to both the basic and acidic FIBROBLAST GROWTH FACTORS but have different amino acid sequences.Extracellular Signal-Regulated MAP Kinases: A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.Integrin alpha6beta1: A cell surface receptor mediating cell adhesion to the EXTRACELLULAR MATRIX and to other cells via binding to LAMININ. It is involved in cell migration, embryonic development, leukocyte activation and tumor cell invasiveness. Integrin alpha6beta1 is the major laminin receptor on PLATELETS; LEUKOCYTES; and many EPITHELIAL CELLS, and ligand binding may activate a number of signal transduction pathways. Alternative splicing of the cytoplasmic domain of the alpha6 subunit (INTEGRIN ALPHA6) results in the formation of A and B isoforms of the heterodimer, which are expressed in a tissue-specific manner.Kidney Tubules, Proximal: The renal tubule portion that extends from the BOWMAN CAPSULE in the KIDNEY CORTEX into the KIDNEY MEDULLA. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the U-shaped LOOP OF HENLE.Transforming Growth Factor alpha: An EPIDERMAL GROWTH FACTOR related protein that is found in a variety of tissues including EPITHELIUM, and maternal DECIDUA. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form which binds to the EGF RECEPTOR.Matrix Metalloproteinase 2: A secreted endopeptidase homologous with INTERSTITIAL COLLAGENASE, but which possesses an additional fibronectin-like domain.Neovascularization, Pathologic: A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.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.Smad1 Protein: A receptor-regulated smad protein that undergoes PHOSPHORYLATION by BONE MORPHOGENETIC PROTEIN RECEPTORS. It regulates BONE MORPHOGENETIC PROTEIN signaling and plays an essential role in EMBRYONIC DEVELOPMENT.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.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.Cell Culture Techniques: Methods for maintaining or growing CELLS in vitro.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Smad7 Protein: An inhibitory smad protein that associates with TRANSFORMING GROWTH FACTOR BETA RECEPTORS and BONE MORPHOGENETIC PROTEIN RECEPTORS. It negatively regulates SIGNAL TRANSDUCTION PATHWAYS by inhibiting PHOSPHORYLATION of RECEPTOR-REGULATED SMAD PROTEINS.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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Cell Line, Tumor: A cell line derived from cultured tumor cells.Mitogen-Activated Protein Kinase 1: A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.Nerve Growth Factors: Factors which enhance the growth potentialities of sensory and sympathetic nerve cells.Animals, Newborn: Refers to animals in the period of time just after birth.Tissue Inhibitor of Metalloproteinase-1: A member of the family of TISSUE INHIBITOR OF METALLOPROTEINASES. It is a N-glycosylated protein, molecular weight 28 kD, produced by a vast range of cell types and found in a variety of tissues and body fluids. It has been shown to suppress metastasis and inhibit tumor invasion in vitro.Vascular Endothelial Growth Factors: A family of angiogenic proteins that are closely-related to VASCULAR ENDOTHELIAL GROWTH FACTOR A. They play an important role in the growth and differentiation of vascular as well as lymphatic endothelial cells.Cartilage: A non-vascular form of connective tissue composed of CHONDROCYTES embedded in a matrix that includes CHONDROITIN SULFATE and various types of FIBRILLAR COLLAGEN. There are three major types: HYALINE CARTILAGE; FIBROCARTILAGE; and ELASTIC CARTILAGE.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/)Oligonucleotide Array Sequence Analysis: Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.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.
  • Idiopathic pulmonary fibrosis (IPF) is a progressive scarring of the lung parenchyma, which ultimately leads to impaired gas exchange, respiratory failure, and death. (springer.com)
  • Idiopathic pulmonary fibrosis. (springer.com)
  • King TE Jr, Pardo A, Selman M. Idiopathic pulmonary fibrosis. (springer.com)
  • Kass DJ, Kaminski N. Evolving genomic approaches to idiopathic pulmonary fibrosis: moving beyond genes. (springer.com)
  • Is idiopathic pulmonary fibrosis an environmental disease? (springer.com)
  • Idiopathic pulmonary fibrosis: a disorder of epithelial cell dysfunction. (springer.com)
  • Short telomeres are a risk factor for idiopathic pulmonary fibrosis. (springer.com)
  • Telomerase mutations in families with idiopathic pulmonary fibrosis. (springer.com)
  • SAN FRANCISCO , Aug. 07, 2017 (GLOBE NEWSWIRE) -- FibroGen, Inc. (NASDAQ:FGEN), a science-based biopharmaceutical company, announced today positive topline results from the company's Phase 2 randomized, double-blind, placebo-controlled study and two combination safety sub-studies of pamrevlumab in patients with idiopathic pulmonary fibrosis (IPF). (corporate-ir.net)
  • Over the past two and a half decades, many clinical trials have been designed to determine the safety and efficacy of pharmacotherapy for patients with idiopathic pulmonary fibrosis (IPF). (ersjournals.com)
  • The evidence-based 2011 clinical practice guidelines for the diagnosis and management of idiopathic pulmonary fibrosis (IPF) [ 1 ] defined IPF as progressive fibrotic lung disease limited to the lungs, occurring in adults without attributable systemic disease and environmental factors. (ersjournals.com)
  • FibroGen's Phase III trial with FG-3019 (pamrevlumab) for idiopathic pulmonary fibrosis (IPF) may face challenges enrolling patients since it does not allow trial participants to be on background therapy with approved drugs, two IPF experts said on the sidelines of the recently concluded American Thoracic Society (ATS) meeting. (pharmaceutical-technology.com)
  • Concentrations of phosphorylated ets-2 were detected via the single and dual immunohistochemical staining of murine lungs and lung sections from patients with idiopathic pulmonary fibrosis. (pubmedcentralcanada.ca)
  • Immunohistochemical staining of lung sections from bleomycin-treated ets-2 (WT/WT) mice and from patients with idiopathic pulmonary fibrosis demonstrated increased staining of phosphorylated ets-2 that colocalized with Type I collagen expression and to fibroblastic foci. (pubmedcentralcanada.ca)
  • The most prevalent form of IIP is idiopathic pulmonary fibrosis (IPF). (pubmedcentralcanada.ca)
  • Pamrevlumab is in Phase 3 clinical development for the treatment of idiopathic pulmonary fibrosis (IPF) and locally advanced unresectable pancreatic cancer (LAPC), and in Phase 2 clinical development for the treatment of Duchenne muscular dystrophy (DMD) and coronavirus (COVID-19). (drugs.com)
  • Pamrevlumab is advancing towards Phase 3 clinical development for the treatment of idiopathic pulmonary fibrosis (IPF) and pancreatic cancer and has been granted Orphan Drug Designation (ODD) in each of these indications, and is currently in a Phase 2 trial for Duchenne muscular dystrophy (DMD). (corporate-ir.net)
  • This new model of pleural fibrosis will allow us to better understand the mechanisms of progressive fibrogenesis, and to explore novel antifibrotic therapies in the pleural cavity. (jimmunol.org)
  • In this review we will discuss the roles of these nuclear co-activators in HSC activation, their mechanism of action in the fibrotic process in the liver and other organs, and the potential of targeting their activity with small molecule drugs for fibrosis reversal. (frontiersin.org)
  • TGFβ1 (transforming growth factor-β1) induces both EMT and fibroblast activation and is considered to be a major pro-fibrotic factor. (biochemsoctrans.org)
  • The most fibrotic drug-induced lesions develop in response to therapy with phenytoin, the least fibrotic lesions are caused by cyclosporin A, and the intermediate fibrosis occurs in nifedipine-induced gingival overgrowth. (hindawi.com)
  • In the late phase of SARS (2-3 weeks), referred as the fibrotic stage, the lungs exhibit dense septal and alveolar fibrosis. (springer.com)
  • Also, the antioxidant response element binding activity of the transcription factor Nrf2 was enhanced by the TA extract in ISO-induced fibrotic rat heart. (imedpub.com)
  • Interstitial pneumonia (IP) refers to involvement of the lung parenchyma by varying degrees of inflammation and fibrosis, in contrast to airspace disease typically seen in bacterial pneumonia. (intechopen.com)
  • The term "Interstitial pneumonia" (IP) is used to describe noninfectious, inflammatory lung disorders characterized by the histologic abnormalities with diffuse interstitial fibrosis involving alveolar walls. (intechopen.com)
  • Studies of patients, cells, and laboratory animals over the last 30 years have led to an ever-increasing corpus of knowledge, based on studies of ever-increasing degrees of sophistication and on the signaling events that occur during lung injury and fibrosis. (springer.com)
  • The growth of lung fibrosis research, coupled with an intense interest on the part of industry to devise therapies, suggests that new therapies are coming that are rationally designed to target these critical signaling events. (springer.com)
  • Pleural fibrosis is a misunderstood disorder which can cause severe restrictive lung disease with high morbidity and even mortality. (jimmunol.org)
  • We further demonstrate that pleural fibrosis can expand into the lung parenchyma from the visceral layer, but not into the muscle from the parietal layer. (jimmunol.org)
  • Pleural fibrosis can cause severe restrictive lung disease. (jimmunol.org)
  • Finally, MWCNTs induced the production of fibrogenic growth factors TGFbeta1 and PDGF that function as paracrine signals to promote the transformation of lung fibroblasts into myofibroblasts, a key molecular step in the development of lung fibrosis. (cdc.gov)
  • The typical clinical feature associated with SARS is diffuse alveolar damage in lung, and lung fibrosis is evident in patients who died from this disease. (springer.com)
  • The mechanisms by which SARS-CoV infection causes lung fibrosis are not fully understood, but transforming growth factor-β (TGF-β) and angiotensin-converting enzyme 2 (ACE2)-mediated lung fibrosis are among the most documented ones. (springer.com)
  • The activation of the TGF-β/Smad pathway is critical to lung fibrosis. (springer.com)
  • The SARS-CoV receptor ACE2 is a negative regulator of lung fibrosis, and SARS-CoV infection decreases ACE2 expression. (springer.com)
  • Therefore, SARS-CoV infection may lead to lung fibrosis through multiple signaling pathways and TGF-β activation is one of the major contributors. (springer.com)
  • The virus can be found in respiratory tract secretions, lung tissue, serum, and stool (Tse et al. (springer.com)
  • The extent of lung fibrosis is positively correlated with the duration of the SARS disease. (springer.com)
  • We challenged ets-2 (A72/A72) transgenic mice (harboring a mutated form of ets-2 at phosphorylation site threonine-72) and ets-2 (wild-type/wild-type [WT/WT]) control mice with sequential intraperitoneal injections of bleomycin, followed by quantitative measurements of lung fibrosis and inflammation and primary cell in vitro assays. (pubmedcentralcanada.ca)
  • The administration of pamrevlumab, a first-in-class anti-connective growth factor monoclonal antibody, could protect the lung from the immediate consequences of the infection presented as acute respiratory distress syndrome. (drugs.com)
  • As tissue scarring progresses, transfer of oxygen into the bloodstream is increasingly impaired, leading to irreversible loss of lung function, as well as high morbidity and mortality rates. (corporate-ir.net)
  • Unexpectedly, KD3010, but not GW501516, showed hepatoprotective and antifibrotic effects in liver fibrosis induced by carbon tetrachloride (CCl 4 ) or bile duct ligation (BDL). (pnas.org)
  • Here we investigated whether the extracts of pomegranate peels (EPP) and seeds (EPS) have preventive efficacy on liver fibrosis induced by carbon tetrachloride (CCl 4 ) in rats and explored its possible mechanisms. (biomedcentral.com)
  • Oxidative stress, cell death, and fibrosis markers were evaluated by molecular biology/biochemical techniques, electron spin resonance spectroscopy, and flow cytometry. (onlinejacc.org)
  • Conclusions Collectively, these results coupled with the excellent safety and tolerability profile of CBD in humans, strongly suggest that it may have great therapeutic potential in the treatment of diabetic complications, and perhaps other cardiovascular disorders, by attenuating oxidative/nitrative stress, inflammation, cell death and fibrosis. (onlinejacc.org)
  • These results demonstrated that MWCNT elicit multiple and intertwining molecular signaling events involving oxidative damage, inflammatory cytokine production, and myofibroblast transformation, which potentially underlie the toxicity and fibrosis in human lungs by MWCNTs. (cdc.gov)
  • A variety of factors have been implicated to produce a second "hit," including hormones derived from adipose tissue (adipocytokines), oxidative stress and gut-derived bacterial endotoxin. (cmaj.ca)
  • RESULTS The retinal vessels of diabetic rats showed differential expression of 20 genes of the transforming growth factor (TGF)-β pathway, in addition to genes involved in oxidative stress, inflammation, vascular remodeling, and apoptosis. (diabetesjournals.org)
  • Liver fibrosis is a feature in the majority of chronic liver diseases and oxidative stress is considered to be its main pathogenic mechanism. (biomedcentral.com)
  • The protective effects of EPP and EPS on biochemical metabolic parameters, liver function, oxidative markers, activities of antioxidant enzymes and liver fibrosis were determined in CCl 4 -induced liver toxicity in rats. (biomedcentral.com)
  • Identification of novel factors that enhance β-cell proliferation and mass regeneration in vivo while retaining optimal function would serve as an ideal strategy for remediation of all forms of diabetes. (diabetesjournals.org)
  • Hyperglycaemia is associated with diffuse thickening of glomerular basement membrane, proliferation and hypertrophy of mesangial cells, podocyte injury, and is a key cause for the loss of glomerular function and the irreversible tubulointerstitial fibrosis [ 3 , 4 ]. (portlandpress.com)
  • Transforming growth factor- β (TGF- β ) is a multifunctional cytokine involved in diverse cellular processes such as cell proliferation, apoptosis, differentiation, and migration [ 8 , 9 ]. (hindawi.com)
  • Our previous study revealed that the flashing light could induce the cell number and activity of posterior sclera cells which resulted in an abnormal proliferation status of sclera in guinea pigs [ 12 ], indicating that active sclera remodeling plays a significant role in the flashing light-induced ocular growth and vision impairment. (hindawi.com)
  • His work has established the central role of the retinal pigment epithelial (RPE) cell in these disorders, and has demonstrated novel mechanisms for growth factor activation of the RPE with resulting alterations in migration, proliferation and gene expression. (usc.edu)
  • Publications] Shimo,T.: 'Inhibition of endogenous expression of connective tissue growth factor by its antisense oligonucleotide and antisense RNA suppresses proliferation and migration of vascular endothelial cells'J.Biochem. (nii.ac.jp)
  • In the medium phase of SARS development (10-14 days), the lungs display fibrous organization including interstitial and airspace fibrosis, reparative fibroblastic proliferation and type II pneumocytic hyperplasia. (springer.com)
  • Despite the significant progress in our understanding of liver fibrosis, the molecular mechanisms through which the extracellular matrix promotes HSC activation are not well understood and no effective therapies have been approved to date that can target this early, reversible, stage in liver fibrosis. (frontiersin.org)
  • This book comprehensively describes the molecular mechanisms of human skin connective tissue aging by emphasizing age-related dermal microenvironment as a strategy for improving our quality of life as well as for preventive and therapeutic intervention of age-related skin diseases. (novapublishers.com)
  • Several new lines of investigation now provide important insight into this area of study and identify two nuclear targets whose inhibition has the potential of reversing liver fibrosis by interfering with HSC activation: Yes-associated protein (YAP), a transcriptional co-activator and effector of the mechanosensitive Hippo pathway, and bromodomain-containing protein 4 (BRD4), an epigenetic regulator of gene expression. (frontiersin.org)
  • Both variants affect nuclear factor binding and may alter gene transcription or transcript stability. (pubmedcentralcanada.ca)
  • Transforming growth factor beta-3 is a protein that in humans is encoded by the TGFB3 gene . (wikipedia.org)
  • marfan syndrome (MFS) is a systemic, autosomal dominant disease of connective tissue cause by mutations in the gene encoding fibrillin-1, a major component of the microfibril network of the ECM ( 13 , 15 ). (physiology.org)
  • Publications] Sasaki,K.: 'Nitric oxide mediates interleukin-1-ianduced gene expression of matrix metalloproteinases and basic fibroblast growth factor in cultured rabbit articular chondrocytes'J.Biochem. (nii.ac.jp)
  • 15 The ligand-activated PPAR functions as a transcription factor and regulates target gene expression. (ahajournals.org)
  • 1988). "Complementary DNA for human glioblastoma-derived T cell suppressor factor, a novel member of the transforming growth factor-beta gene family" . (wikidoc.org)
  • Platelet-derived growth factor (PDGF) was discovered as a major mitogenic factor present in serum but absent from plasma. (rndsystems.com)
  • Serum components fibronectin and platelet-derived growth factor (PDGF) are strong chemoattractants for other RPE cells, astrocytes, and fibrocytes. (medscape.com)
  • Hypoxia occurs when tumor growth exceeds the ability of blood vessels to supply the tumor with oxygenated blood. (stanford.edu)
  • Current methods for measuring hypoxia include invasive procedures such as tissue biopsy, or insertion of an electrode into the tumor. (stanford.edu)
  • To determine whether PPARδ agonists are beneficial in experimental liver fibrosis, mice were treated orally with a PPARδ agonist, KD3010, or with the well-validated PPARδ agonist GW501516. (pnas.org)
  • Connective tissue growth factor and bone morphogenetic protein 2 are induced following myocardial ischemia in mice and humans. (uio.no)
  • Recently, IGFBP-5 [IGF (insulin-like growth factor)-binding protein-has also been shown to induce similar effects on TGFβ1, and is strongly implicated in the process of senescence. (biochemsoctrans.org)
  • Calcium-Sensing Receptor on Neutrophil Promotes Myocardial Apoptosis and Fibrosis After Acute Myocardial Infarction via NLRP3 Inflammasome Activation. (amedeo.com)
  • Liver fibrosis is the result of a deregulated wound healing process characterized by the excessive deposition of extracellular matrix. (frontiersin.org)
  • 4 5 6 7 8 9 As well as stimulating the formation of scar tissue, these factors mediate subsequent wound contracture. (arvojournals.org)
  • Wound healing involves a coordinated series of tissue movements that bears a striking resemblance to various embryonic morphogenetic episodes. (biologists.org)
  • For both naturally occurring and wound-activated tissue movements, JNK signalling appears to be crucial, as does the tight regulation of associated cell divisions and adhesions. (biologists.org)
  • But a dramatic reawakening of the tissue building machinery is required if the organism is wounded, in order to replace missing tissues and repair the wound. (biologists.org)
  • It also discusses how studies of morphogenesis have shed light on the ways that cell:cell adhesions and cell division might be regulated as tissues move and knit together in a wound situation. (biologists.org)
  • Whenever an organism sustains an injury, especially to its outer protective skin layer, it must act rapidly to repair the wound to prevent further blood and tissue loss and infection. (biologists.org)
  • The deeper connective tissue is replaced by activated fibroblasts at the wound edge that proliferate and then migrate into the wound bed to form a granulation tissue (so named because of its granular appearance due to massive invasion by capillary networks), which contracts to aid in closing the wound margins. (biologists.org)
  • Neutrophils and macrophages (blue) emigrate from the wound capillaries into the wound granulation tissue where they kill microbes, engulf cell and matrix debris, and release signals that act on the host wound tissues. (biologists.org)
  • These protective effects were accompanied by an overall improvement in cardiomyocyte architecture and a massive reduction of myocardial fibrosis with a concomitant amelioration of inflammation. (biologists.org)
  • aB-Crystallin Regulates Subretinal Fibrosis by Modulation of Epithelial-Mesenchymal Transition Am J Pathol. (usc.edu)
  • 2003 ). The mechanism of DAD is believed to be endothelial and alveolar epithelial injury due to both direct viral effects and other indirect factors (Nicholls et al. (springer.com)
  • At the same time, fibrous tissue could be detected in alveolar spaces. (springer.com)
  • Results Bevacizumab accelerated fibrosis in patients with proliferative membranes. (bmj.com)
  • In particular, he is interested in how alterations in the retinal microenvironment can promote the development of intraocular fibrosis, proliferative membranes and neovascular choroidal responses. (usc.edu)
  • In conclusion, our data demonstrate that an orally active PPARδ agonist has hepatoprotective and antifibrotic effects in animal models of liver fibrosis, suggesting a possible mechanistic and therapeutic approach in treating patients with chronic liver diseases. (pnas.org)
  • MicroRNA-29 family, a crucial therapeutic target for fibrosis diseases. (semanticscholar.org)
  • Most recently, Dr Hinton's lab has been evaluating endogenous neuroprotectants (eg pigment epithelial derived factor) and chaperones (alpha B crystallin) for their therapeutic potential. (usc.edu)
  • Different circulating markers and Micro-RNAs as novel diagnostic and therapeutic tools in HCV-induced liver fibrosis and hepatocellular carcinoma. (aucegypt.edu)
  • These data strongly suggest that AAV/hSMAD3 delivery gave anti-atherosclerosis therapeutic effect without the expected undesirable effect of TGFβ1-associated fibrosis. (biomedcentral.com)
  • One of this markers, the paraneoplastic antigen Ma2 (PNMA2), which is normally expressed only in nervous tissue, can in the process of carcinogenesis be detected in tumors located outside the nervous system. (enets.org)
  • The hepatoprotective and antifibrotic effect of KD3010 was confirmed in a model of cholestasis-induced liver injury and fibrosis using bile duct ligation for 3 wk. (pnas.org)
  • Prolonged hyperglycaemia plays a crucial role during the diabetic nephropathy development because of its effects in modifying the activities of multiple signalling pathways and transcription factors in mesangial cells and podocytes, which are essential in maintaining the glomerular capillary structure and regulating glomerular filtration. (portlandpress.com)
  • As early mesangial matrix expansion and the later chang- growth factors commonly control essential biological es of fibrosis in advanced diabetic nephropathy . (deepdyve.com)
  • Several studies have shown that the higher prevalence of HCV infection in diabetic patients is not related to the main risk factors associated with HCV seropositivity ( 17 , 18 , 22 , 24 ). (diabetesjournals.org)
  • In addition, the prevalence of chronic hepatitis B virus (HBV) infection, which shares similar epidemiological factors of transmision with HCV, has not been found higher in type 2 diabetic patients than in the general population ( 19 , 21 , 22 , 25 , 26 ). (diabetesjournals.org)
  • in particular, the factors that lead to progressive hepatocellular damage after triglyceride accumulation are not well elucidated. (cmaj.ca)