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 126.96.36.199.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.
"Role and interaction of connective tissue growth factor with transforming growth factor-beta in persistent fibrosis: A mouse ... "Selective expression of connective tissue growth factor in fibroblasts in vivo promotes systemic tissue fibrosis". Arthritis ... Brigstock DR (March 2010). "Connective tissue growth factor (CCN2, CTGF) and organ fibrosis: lessons from transgenic animals". ... cleave connective tissue growth factor and reactivate angiogenic activity of vascular endothelial growth factor 165". J. Biol. ...
TGF beta 2
1999). "Role and interaction of connective tissue growth factor with transforming growth factor-beta in persistent fibrosis: A ... 1992). "Molecular cloning and structure of the human transforming growth factor-beta 2 gene promoter". Growth Factors. 4 (4): ... Transforming growth factor-beta 2 (TGF-β2) is a secreted protein known as a cytokine that performs many cellular functions and ... 1988). "Transforming growth factor-beta 2: cDNA cloning and sequence analysis". DNA. 7 (1): 1-8. doi:10.1089/dna.1988.7.1. PMID ...
RXi's first sd-rxRNA candidate, RXI‑109, is designed to reduce the expression of connective tissue growth factor, a critical ... "Evaluating RXI-109 to Reduce the Progression of Subretinal Fibrosis in Subjects With NVAMD". Clinicaltrials.gov. U.S. National ... regulator of biological pathways involved in fibrosis, including scar formation in the skin. The product has been in several ...
... connective tissue growth factor or CCN2), and NOV (nephroblastoma overexpressed or CCN3). Together with three Wnt-induced ... They are also involved in biological processes including angiogenesis, inflammation, fibrosis, wound healing and tumorigenesis ... connective tissue growth factor) CCN3: NOV (nephroblastoma overexpressed) CCN4: WISP1 (WNT1 inducible signaling pathway protein ... which include the insulin-like growth factor-binding domain (IGFBP), the Von Willebrand factor type C domain (VWC), the ...
Transforming growth factor, beta 3
"Role and interaction of connective tissue growth factor with transforming growth factor-beta in persistent fibrosis: A mouse ... "Entrez Gene: TGFB3 transforming growth factor, beta 3". Herpin A, Lelong C, Favrel P (May 2004). "Transforming growth factor- ... "Transforming growth factor-beta, transforming growth factor-beta receptor II, and p27Kip1 expression in nontumorous and ... Transforming growth factor beta-3 is a protein that in humans is encoded by the TGFB3 gene. It is a type of protein, known as a ...
Transforming growth factor, beta 3
"Role and interaction of connective tissue growth factor with transforming growth factor-beta in persistent fibrosis: A mouse ... transforming growth factor beta receptor binding. • growth factor activity. • transforming growth factor beta binding. • type ... type III transforming growth factor beta receptor binding. • cytokine activity. • type I transforming growth factor beta ... TGFB3, ARVD, ARVD1, RNHF, TGF-beta3, Transforming growth factor, beta 3, LDS5, transforming growth factor beta 3. ...
WNT1-inducible-signaling pathway protein 2
... connective tissue growth factor, or CCN2), and NOV. These proteins, together with WISP1/CCN4, WISP2 (CCN5, this gene), and ... WISP-2 also inhibits cardiac hypertrophy and fibrosis, an effect that appears linked to the absence of the CT domain. GRCh38: ... Lake AC, Bialik A, Walsh K, Castellot JJ (Jan 2003). "CCN5 is a growth arrest-specific gene that regulates smooth muscle cell ... Mason HR, Lake AC, Wubben JE, Nowak RA, Castellot JJ (Mar 2004). "The growth arrest-specific gene CCN5 is deficient in human ...
WNT1-inducible-signaling pathway protein 1
... connective tissue growth factor, Cyr61/Cef10, and neuroblastoma overexpressed gene) family, suppresses In vivo tumor growth and ... WISP-1 is upregulated in human patients with idiopathic pulmonary fibrosis and in a mouse model of bleomycin-induced lung ... Xie D, Nakachi K, Wang H, Elashoff R, Koeffler HP (Dec 2001). "Elevated levels of connective tissue growth factor, WISP-1, and ... "Overexpression of connective tissue growth factor WISP-1 in Chinese primary rectal cancer patients". World Journal of ...
... mesangial cells can respond by producing several growth factors: TGF-1, VEGF and connective tissue growth factor. The mesangium ... mesangial matrix expansion then glomerulosclerosis and fibrosis. Mesangial pathologies may also develop during the early phase ... Mice lacking the growth factor PDGF-B or PDGFRβ do not develop mesangial cells. When mesangial cells are absent the blood ... Endothelial precursor cells secrete platelet-derived growth factor (PDGF)-B and mesangial cells have receptors for PDGF. This ...
... leads to replacement of the hematopoietic tissue of the bone marrow by connective tissue via collagen fibrosis. The decrease in ... The V617F mutation appears to make hematopoietic cells more sensitive to growth factors that need JAK2 for signal transduction ... Production of cytokines such as fibroblast growth factor by the abnormal hematopoietic cell clone (particularly by ... Myelofibrosis is a form of myeloid metaplasia, which refers to a change in cell type in the blood-forming tissue of the bone ...
Pancreatic stellate cell
Connective tissue growth factor is involved in the pathogenesis of fibrotic diseases and is predominantly found in PaSCs ... While the pathogenesis of fibrosis remains elusive, the activation of stellate cells contribute to pancreatic fibrosis. ... The production of these factors is regulated by fibroblast growth factor 2, TGF-β1, and PDGF. In addition to cytokine-mediated ... Protein kinases such as MAPKs are primary mediators of activating signals initiated by the growth factors, angiotensin II and ...
... and fibroblast growth factors, which are important in the inflammation and fibrosis of CWP. Aggregations of carbon-laden ... residing in the connective tissue or pulmonary lymph nodes. Coal dust provides a sufficient stimulus for the macrophage to ... These aggregations can cause inflammation and fibrosis, as well as the formation of nodular lesions within the lungs. The ... Pathologically, these consist of fibrosis with haphazardly-arranged collagen and many pigment-laden macrophages and abundant ...
... is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This ... Other soluble mediators of fibrosis include CTGF, platelet-derived growth factor (PDGF), and Interleukin 4 (IL-4). These ... Fibrosis is similar to the process of scarring, in that both involve stimulated fibroblasts laying down connective tissue, ... Physiologically, fibrosis acts to deposit connective tissue, which can obliterate the architecture and function of the ...
... certain genetic factors, and exposure to silica. The underlying mechanism involves the abnormal growth of connective tissue ... Nephrogenic systemic fibrosis, a condition usually caused by kidney failure that causes fibrosis (thickening) of the tissues. ... Dysregulated transforming growth factor β (TGF-β) signalling in fibroblasts and myofibroblasts has been observed in multiple ... T cells differentiate into subsets, including Th2 cells, which play a vital role in tissue fibrosis. Anti-topoisomerase 1 ...
... in excessive fibrosis are not fully understood but there is evidence that supports involvement from local growth factors FGF-2 ... Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol 2002; 3:349-363 Boluyt MO, ... Adenovirusmediated overexpression of human transforming growth factor-beta 1 in rat cardiac fibroblasts, myocytes and smooth ... TGF-beta and platelet-derived growth factor. TGF-β1 plays an important role in cardiac remodelling through the stimulation of ...
... resulting in fibrosis and the formation of connective tissue in the medullary cavity of the affected bone. Pain may be caused ... The cause is unknown, but genetics, stress, infection, metabolism, or an autoimmune component may be factors. It has also been ... suggested that rapid growth and high-protein food are involved in the pathogenesis. Panosteitis is characterized histologically ...
In nerve cells, axonal growth is mediated by nerve growth factor in a haptotactic manner, where the axon of nerve cells grows ... which can differentiate into different kinds of connective tissue in the wound healing process. The haptotaxis is mediated by ... Idiopathic pulmonary fibrosis (IPF) is a disease marked by fibrosis in lung mesothelial cells. TGF-β1 is a cytokine found in ... Taniuchi, M.; Clark, H. B.; Johnson, E. M. (1986). "Induction of nerve growth factor receptor in Schwann cells after axotomy". ...
... means of sealing tissue than current tissue sealants due to the robust nature of collagen which makes up connective tissue. A ... Like corneal fibroblasts, dermal fibroblast proliferation can be stimulated by the presence of fibroblast growth factor (FGF). ... This contraction plays a critical role in wound healing and fibrosis. By pulling tissues closed differentiated myofibroblasts, ... Furthermore, dermal fibroblasts create long fibrous bands of connective tissue which anchor the skin to the fascia of the body ...
Xie D, Nakachi K, Wang H, Elashoff R, Koeffler HP (2001). "Elevated levels of connective tissue growth factor, WISP-1, and ... However, excessive matrix deposition can lead to fibrosis, scarring, and loss of tissue function. In skin wounds, CYR61 ... including stimulation by platelet-derived growth factor and basic fibroblast growth factor, transforming growth factor β1 (TGF- ... connective tissue growth factor, or CCN2), and NOV (nephroblastoma overexpressed, or CCN3). These proteins, together with WISP1 ...
The cytokines, transforming growth factor beta and tumor necrosis factor alpha, appear to play major roles in the development ... Macrophages phagocytose (ingest) the fibers and stimulate fibroblasts to deposit connective tissue. Due to the asbestos fibers ... fibrosis). External agents/. occupational. lung disease. Pneumoconiosis Aluminosis. Asbestosis. Baritosis. Bauxite fibrosis. ... "Transforming Growth Factor-β1 overexpression in Tumor Necrosis Factor-α receptor knockout mice induces fibroproliferative lung ...
Nerve growth factors and nerve grafts can also be used to increase the speed of the regenerative process. Perineurial repair ... Trauma to the nerve by cutting out each fascicle and fibrosis, a build up of tissue as a reaction, that develops due to the ... A nerve injury in continuity results when axonal function is nonexistent but the structure of the connective tissue is ... Cells from bone marrow, mesenchymal stem cells, have been shown to secrete growth factors and produce myelin genes when grown ...
Each type of connective tissue in animals has a type of ECM: collagen fibers and bone mineral comprise the ECM of bone tissue; ... In addition, it sequesters a wide range of cellular growth factors and acts as a local store for them. Changes in physiological ... Formation of the extracellular matrix is essential for processes like growth, wound healing, and fibrosis. An understanding of ... Proteoglycans may also help to trap and store growth factors within the ECM. Described below are the different types of ...
National Institute of Arthritis and Musculoskeletal and Skin Diseases
... studies related to wound healing and fibrosis; heritable disorders of connective tissue (such as Marfan syndrome); studies ... growth factors and cytokines on bone cells. The programs emphasize the application of fundamental knowledge of bone cell ... Laboratory of Oral Connective Tissue Biology-studies the molecular biology of dental-oral-craniofacial development, with a ... The program operates a Laboratory of Regenerative Medicine and a Laboratory of Oral Connective Tissue Biology. NIAMS scientists ...
Its absence may lead to defects in the transforming growth factor beta superfamily of proteins, which control cell growth and ... Thus, not only is LOX crucial to cardiovascular development, it is thought to play a major role in connective tissue ... Data derived from a mouse model of myelofibrosis implicated LOX in bone marrow fibrosis. In a rodent model of breast cancer, a ... Subcutaneous tumor-derived LOX was shown to increase vascular endothelial growth factor (VEGF) expression and secretion, which ...
The expression of MMP7 is regulated by the Wnt/ β catenin signaling pathway, and mediated by transformation growth factor β ( ... that the proteolytic activity of MMP7 plays major role in tissue remodeling in biliary atresia-associated liver fibrosis. MMP7 ... expression facilitates cancer invasion and angiogenesis by degrading extracellular matrix macromolecules and connective tissues ... and epidermal growth factor (EGF). In addition, the high level expression of AP-1 and its binding proteins were found to be ...
It is reported that several genes are regulated by YAP1, including Birc2, Birc5, connective tissue growth factor (CTGF), ... "Peptide binding consensus of the NHE-RF-PDZ1 domain matches the C-terminal sequence of cystic fibrosis transmembrane ... Zhao B, Kim J, Ye X, Lai ZC, Guan KL (February 2009). "Both TEAD-binding and WW domains are required for the growth stimulation ... Vassilev A, Kaneko KJ, Shu H, Zhao Y, DePamphilis ML (May 2001). "TEAD/TEF transcription factors utilize the activation domain ...
regulation of cellular response to growth factor stimulus. • protein kinase A signaling. • activation of protein kinase A ... Marfan syndrome (MFS) is an autosomal dominant disorder that affects the connective tissues of bodily systems such as the eyes ... cellular response to transforming growth factor beta stimulus. • skeletal system development. • kidney development. • embryonic ... 1apj: NMR STUDY OF THE TRANSFORMING GROWTH FACTOR BETA BINDING PROTEIN-LIKE DOMAIN (TB MODULE/8-CYS DOMAIN), NMR, 21 STRUCTURES ...
Sp1 is a transcription factor most closely studied in this context. Apart from TGFβ, connective tissue growth factor (CTGF) has ... This form, nephrogenic fibrosing dermopathy or nephrogenic systemic fibrosis, has been linked to exposure to ... Systemic scleroderma, also called diffuse scleroderma or systemic sclerosis, is an autoimmune disease of the connective tissue ... A significant player in the process is transforming growth factor (TGFβ). This protein appears to be overproduced, and the ...
Connective tissue growth factor is a regulator for fibrosis in human chronic pancreatitis
Background: Connective tissue growth factor (CTGF), which is regulated by transforming growth factor beta (TGF-beta), has ... Connective tissue growth factor is a regulator for fibrosis in human chronic pancreatitis Ann Surg. 1999 Jul;230(1):63-71. doi ... Moreover, CTGF mRNA expression levels correlated positively with the degree of fibrosis in CP tissues. ... Tissue samples of 25 previously healthy organ donors (12 women, 13 men) served as controls. The expression of TGF-beta1, TbetaR ...
Inhibition of connective tissue growth factor by siRNA prevents liver fibrosis in rats - Li - 2006 - The Journal of Gene...
Deletion of connective tissue growth factor ameliorates peritoneal fibrosis by inhibiting angiogenesis and inflammation
Bone Morphogenetic Protein-6 and Connective Tissue Growth Factor in Renal Fibrosis
... DSpace/Manakin Repository. ... and the profibrotic connective tissue growth factor (CTGF) in renal fibrogenesis, via experimental and human studies. Data are ... There was also increased tubulointerstitial damage and an altered, profibrotic growth factor profile. Exploring the mechanisms ... To study the effects of genetic CTGF attenuation on fibrosis in the context of chronic and severe renal injury, transgenic ...
Connective Tissue Growth Factor (CTGF) expression in response to injury mediates matrix deposition in bleomycin-induced lung...
... expression in response to injury mediates matrix deposition in bleomycin-induced lung fibrosis. In: ARTHRITIS AND RHEUMATISM. ( ... Connective Tissue Growth Factor (CTGF) expression in response to injury mediates matrix deposition in bleomycin-induced lung ... Connective Tissue Growth Factor (CTGF) expression in response to injury mediates matrix deposition in bleomycin-induced lung ... Connective Tissue Growth Factor (CTGF) ... fibrosis.. Event:. 66th Annual Scientific Meeting of the ...
Serval - Connective tissue growth factor, steatosis and fibrosis in patients with chronic hepatitis C.
Connective tissue growth factor expression was higher in patients with steatosis (P=0.039) and in patients with fibrosis (P= ... Connective tissue growth factor (CTGF) plays a major role in extracellular matrix production in fibrotic disorders including ... We hypothesized that CTGF may link steatosis, insulin resistance and fibrosis. METHODS: We included 153 chronic hepatitis C ... Both steatosis and insulin resistance have been linked to accelerated fibrosis in chronic hepatitis C. ...
Signalling and regulation of collagen I synthesis by ET-1 and TGF-β1 - Horstmeyer - 2005 - The FEBS Journal - Wiley Online...
ET-1 further induced connective tissue growth factor (CTGF), as did TGF-β1, however, to lower levels. While rapid and sustained ... Role of endothelin-1/endothelin receptor signaling in fibrosis and calcification in nephrogenic systemic fibrosis, Experimental ... Tsuyoshi Shimo, Akira Sasaki, Mechanism of cancer-induced bone destruction: An association of connective tissue growth factor ( ... The regulation of connective tissue growth factor expression influences the viability of human trabecular meshwork cells, ...
Interstitial Pneumonia Associated with Connective Tissue Disease: An Overview and an Insight | IntechOpen
One of the major categories of disorders frequently associated with IP is a connective tissue disease (CTD), in which ... autoimmune-mediated tissue injury leads to multiple organ impairment. Today, IP represents the most critical pulmonary ... refers to involvement of the lung parenchyma by varying degrees of inflammation and fibrosis, in contrast to airspace disease ... and insulin-like growth factor (IGF-1), which leads to activation of fibroblasts, resulting in the development of fibrosis [12 ...
Connective Tissue Growth Factor Is Crucial to Inducing a Profibrotic Environment in "Fibrosis-Resistant" Balb/c Mouse Lungs
A novel integrin α5β1 binding domain in module 4 of connective tissue growth factor (CCN2/CTGF) promotes adhesion and migration...
di Mola FF, Friess H, Martignoni ME, et al. Connective tissue growth factor is a regulator for fibrosis in human chronic ... connective tissue growth factor. Connective tissue growth factor (CCN2, also termed CTGF) is one of six structurally related ... Background: Connective tissue growth factor (CCN2) is upregulated in pancreatic fibrosis and desmoplastic pancreatic tumours. ... di Mola FF, Friess H, Riesle E, et al. Connective tissue growth factor is involved in pancreatic repair and tissue remodeling ...
Cellular and molecular mechanisms of renal fibrosis. - PubMed - NCBI
... connective tissue growth factor; ECM, extracellular matrix; FGF2, basic fibroblast growth factor; GSK3β, glycogen synthase ... connective tissue growth factor; EMT, epithelial-mesenchymal transition; FGF2, basic fibroblast growth factor; MCP1, monocyte ... T cell factor; TGF-β1, transforming growth factor β1; TβR1, type I TGF-β receptor; TβRII, type II TGF-β receptor; tPA, tissue- ... transforming growth factor β1; TNF, tumor necrosis factor; tPA, tissue-type plasminogen activator. ...
JCI - The von Hippel-Lindau Chuvash mutation promotes pulmonary hypertension and fibrosis in mice
... connective tissue growth factor (Ctgf); lysyl oxidase (Lox) (67); and fibronectin (Fn1). Further supporting this, Fn1 mRNA ... Hypoxia-inducible factor signaling in the development of tissue fibrosis. Cell Cycle. 2008;7(9):1128-1132.. View this article ... Schultz K, Fanburg BL, Beasley D. Hypoxia and hypoxia-inducible factor-1alpha promote growth factor-induced proliferation of ... and platelet-derived growth factor-β (PDGFB), promotes pulmonary hypertension, inflammation, and fibrosis in animal models and ...
Connective Tissue Growth Factor Modulates Adult β-Cell Maturity and Proliferation to Promote β-Cell Regeneration in Mice |...
Connective tissue growth factor is a regulator for fibrosis in human chronic pancreatitis. Ann Surg 1999;230:63-71pmid:10400038 ... Connective tissue growth factor: structure-function relationships of a mosaic, multifunctional protein. Growth Factors 2008;26: ... Regulation of pancreatic function by connective tissue growth factor (CTGF, CCN2). Cytokine Growth Factor Rev 2013;24:59-68pmid ... Connective tissue growth factor gene regulation. Requirements for its induction by transforming growth factor-beta 2 in ...
Ras-Related Associated with Diabetes | SpringerLink
Towards better definition, quantification and treatment of fibrosis in heart failure. A scientific roadmap by the Committee of...
Illustration: Maartje Kunen, Medical Visuals.) AngII, angiotensin II; CTGF, connective tissue growth factor; DAMPS, danger‐ ... derived growth factor; TGF, transforming growth factor; TIMP, tissue inhibitor of metalloproteinase; TNF, tumour necrosis ... Fibrosis is a pivotal player in heart failure development and progression. Measurements of (markers of) fibrosis in tissue and ... and intrinsic tissue changes during aging and senescence. The aetiological factors underpinning fibrosis, as well as the ( ...
The Functional and Clinicopathological Roles and Therapeutic Implication of Connective Tissue Growth Factor in Peritoneal...
... and fibrosis. Recent studies showed that overexpression of CTGF in human oral squamous cell carcinoma reduces cell growth and ... The Functional and Clinicopathological Roles and Therapeutic Implication of Connective Tissue Growth Factor in Peritoneal ... The Functional and Clinicopathological Roles and Therapeutic Implication of Connective Tissue Growth Factor in Peritoneal ... Cancer tissue and adjacent normal tissue Urine Blood serum and blood plasma ...
Connective tissue growth factor(CCN2), a pathogenic factor in diabetic nephropathy. What does it do? How does it do it?
Its expression is induced by a number of factors including TGF-β. It has been associated with fibrosis in various tissues ... Connective tissue growth factor(CCN2), a pathogenic factor in diabetic nephropathy. What does it do? How does it do it?. ... Connective tissue growth factor (CTGF/CCN2) is a member of the CCN family of matricellular proteins. ... It can promote TGF-β signalling by binding directly to the growth factor, promoting its interaction with the TGF-β receptor; by ...
Protection from liver fibrosis by a peroxisome proliferator-activated receptor δ agonist | PNAS
2008) Connective tissue growth factor: A fibrogenic master switch in fibrotic liver diseases. Liver Int 28:1065-1079. ... Interestingly, connective tissue growth factor (CTGF) was induced by GW501516 but not by KD3010. We therefore compared hepatic ... Interestingly, profibrogenic connective tissue growth factor was induced significantly by GW501516, but not by KD3010, ... S3B). Hepatocyte growth factor (HGF) was induced in KD3010-treated hepatic stellate cells compared with control cells (Fig. S3B ...
CTGF - Wikipedia
"Role and interaction of connective tissue growth factor with transforming growth factor-beta in persistent fibrosis: A mouse ... "Selective expression of connective tissue growth factor in fibroblasts in vivo promotes systemic tissue fibrosis". Arthritis ... Brigstock DR (March 2010). "Connective tissue growth factor (CCN2, CTGF) and organ fibrosis: lessons from transgenic animals". ... cleave connective tissue growth factor and reactivate angiogenic activity of vascular endothelial growth factor 165". J. Biol. ...
Effects of Antiproteinuric Intervention on Elevated Connective Tissue Growth Factor (CTGF/CCN-2) Plasma and Urine Levels in...
Selective expression of connective tissue growth factor in fibroblasts in vivo promotes systemic tissue fibrosis. Arthritis ... Transforming growth factor-beta/connective tissue growth factor axis in the kidney. Int J Biochem Cell Biol 40: 9-13, 2008. ... Role of connective tissue growth factor in profibrotic action of transforming growth factor-beta: A potential target for ... Connective tissue growth factor is a mediator of angiotensin II-induced fibrosis. Circulation 108: 1499-1505, 2003. ...
Frontiers | Targeting Mechanotransduction at the Transcriptional Level: YAP and BRD4 Are Novel Therapeutic Targets for the...
Despite the significant progress in our understanding of liver fibrosis, the molecular mechanisms through which the ECM ... However, chronic liver damage leads to perpetual HSC activation, progressive formation of pathological scar tissue and, ... Despite the significant progress in our understanding of liver fibrosis, the molecular mechanisms through which the ECM ... However, chronic liver damage leads to perpetual HSC activation, progressive formation of pathological scar tissue and, ...
Expression of Connective Tissue Growth Factor after Glaucoma Filtration Surgery in a Rabbit Model | IOVS | ARVO Journals
purpose. Connective tissue growth factor (CTGF) appears to play a significant role in mediating fibrosis in several tissues. To ... Transforming growth factor beta induces anchorage-independent growth of NRK fibroblasts via a connective tissue growth factor- ... Connective tissue growth factor: a mediator of TGF-beta action on fibroblasts (review). Cytokine Growth Factor Rev. 1997;8:171- ... Connective tissue growth factor gene regulation: requirements for its induction by transforming growth factor-beta 2 in ...
Vascular Endothelial Growth Factor Reduced and Connective Tissue Growth Factor Induced by Triamcinolone in ARPE19 Cells under...
Connective tissue growth factor (CTGF/CCN2) in hepatic fibrosis. Hepatol Res. 2003;26:1-9. [CrossRef] [PubMed] ... Hepatocyte growth factor counteracts transforming growth factor-beta1, through attenuation of connective tissue growth factor ... Effect of transforming growth factor-beta on activity of connective tissue growth factor gene promoter in mouse NIH/3T3 ... Vascular Endothelial Growth Factor Reduced and Connective Tissue Growth Factor Induced by Triamcinolone in ARPE19 Cells under ...
MicroRNA-29 family, a crucial therapeutic target for fibrosis diseases. - Semantic Scholar
... renal fibrosis, pulmonary fibrosis, cardiac fibrosis. In this review, we are discussing the comprehensive role of miR-29 family ... Fibrosis is the leading cause of organ dysfunction in diseases and results from an imbalance in the turnover of extracellular ... Accumulating studies have demonstrated that miR-29 family participates in the development of liver fibrosis, ... in moderating profibrotic effect and its potential as therapeutic approach to fibrosis diseases. ...
Variants of CTGF are associated with hepatic fibrosis in Chinese, Sudanese, and Brazilians infected with Schistosomes
Connective tissue growth factor (CTGF/CCN2) in hepatic fibrosis. Hepatol. Res. 26:1-9 10.1016/S1386-6346(03)00115-3 [PubMed] [ ... Inhibition of connective tissue growth factor by siRNA prevents liver fibrosis in rats. J. Gene Med. 8:889-900 10.1002/jgm.894 ... connective tissue growth factor. ECMP. extracellular matrix protein. HBV. hepatitis B virus. HF. hepatic fibrosis. OR. odds ... Connective tissue growth factor and progressive fibrosis in biliary atresia. Pediatr. Surg. Int. 21:12-16 10.1007/s00383-004- ...
Fibrotic Signaling in the Lung | SpringerLink
Idiopathic pulmonary fibrosis (IPF) is a progressive scarring of the lung parenchyma, which ultimately leads to impaired gas ... alveolar epithelial cells initiate fibrosis through autocrine and paracrine secretion of connective tissue growth factor. Am J ... CXCL12 induces connective tissue growth factor expression in human lung fibroblasts through the Rac1/ERK, JNK, and AP-1 ... Gene expression profiling of connective tissue growth factor (CTGF) stimulated primary human tenon fibroblasts reveals an ...
Connective tissue growth factor overexpression in cardiomyocytes promotes cardiac hypertrophy and protection against pressure...
Surprisingly, cardiac tissues of both models did not show increased fibrosis or enhanced gene expression of fibrotic markers. ... Connective tissue growth factor (CTGF) is a secreted protein that is strongly induced in human and experimental heart failure. ... Connective tissue growth factor overexpression in cardiomyocytes promotes cardiac hypertrophy and protection against pressure ... To investigate CTGF as a fibrosis inducer, we performed morphological and gene expression analyses of CTGF-TG mice and rat ...
JCI - Specialized fibroblast differentiated states underlie scar formation in the infarcted mouse heart
Adenoviral gene transfer of connective tissue growth factor in the lung induces transient fibrosis. Am J Respir Crit Care Med. ... In addition to regulating local fibrosis and ECM production, fibroblasts also secrete growth factors to support tissue ... Deletion of periostin reduces muscular dystrophy and fibrosis in mice by modulating the transforming growth factor-β pathway. ... Skin flap-induced regression of granulation tissue correlates with reduced growth factor and increased metalloproteinase ...
The Molecular Basis for the Aging of Human Skin | Nova Science Publishers
Regulation and function of connective tissue growth factor/CCN2 in tissue repair, scarring and fibrosis. Cytokine Growth Factor ... Regulation and function of connective tissue growth factor/CCN2 in tissue repair, scarring and fibrosis. Cytokine Growth Factor ... Tumor necrosis factor alpha suppresses the induction of connective tissue growth factor by transforming growth factor-beta in ... Tumor necrosis factor alpha suppresses the induction of connective tissue growth factor by transforming growth factor-beta in ...
The Impact of Delflex on Mesothelial Cell Viability and Peritoneal Transport - Full Text View - ClinicalTrials.gov
Connective tissue growth factor (CTFG) may be another marker of peritoneal membrane fibrosis and thus predictive of dialysis ... Connective tissue growth factor(CTGF)in spent dialysis fluid [ Time Frame: 6 months ]. Connective tissue growth factor (CTGF) ... Connective tissue growth factor and its regulation in the peritoneal cavity of peritoneal dialysis patients. Kidney Int. 2003 ... Cancer Antigen 125 (CA125)levels (indicative of mesothelial cell mass) and connective tissue growth factor (CTGF) levels (a ...
CTGFIdiopathic pulmonarCCN2CollagenAngiogenesisCardiacRenalPulmonaryFibrogenesisFibroticHepatic fibrosisProgressionLungLiver fibrosis induced by carbon tetrachlorideTubular atrophy and interstitial fibrosisOxidativeSignaling pathwaysProliferationProteinsCytokinesMechanismsPancreaticGeneRole in the pathogenesisPlatelet-deriveProfibroticInhibitionPathogenesisTumorDermalMiceCirrhosisVascularInducePromotesGenesWoundDepositionDysfunctionMolecularMyocardial fibrosisSubretinal fibrosisAlveolarMembranesTherapeuticMarkersInflammation and fibrosisInjury and fibrosisDiabeticHepatocellular
- Connective tissue growth factor (CTGF), which is regulated by transforming growth factor beta (TGF-beta), has recently been implicated in skin fibrosis and atherosclerosis. (nih.gov)
- In the present study, the authors analyzed the concomitant presence of TGF-beta1 and its signaling receptors-TGF-beta receptor I, subtype ALK5 (TbetaR-I(ALK5)), and TGF-beta receptor II (TbetaR-II)-as well as CTGF and collagen type I in the pancreatic tissue of patients undergoing surgery for chronic pancreatitis. (nih.gov)
- Northern blot analysis showed that CP tissue samples exhibited concomitant enhanced mRNA expression of TGF-beta1 (38-fold), TbetaR-II (5-fold), CTGF (25-fold), and collagen type I (24-fold) compared with normal controls. (nih.gov)
- Moreover, CTGF mRNA expression levels correlated positively with the degree of fibrosis in CP tissues. (nih.gov)
- In this thesis, we focus on the role of the antifibrotic bone morphogenetic proteins (BMPs, particularly BMP-6) and the profibrotic connective tissue growth factor (CTGF) in renal fibrogenesis, via experimental and human studies. (uu.nl)
- To study the effects of genetic CTGF attenuation on fibrosis in the context of chronic and severe renal injury, transgenic CTGF+/- and wild-type CTGF+/+ mice were subjected to models of long-term diabetes (6 months), UUO and aristolochic acid nephropathy. (uu.nl)
- Connective Tissue Growth Factor (CTGF) expression in response to injury mediates matrix deposition in bleomycin-induced lung fibrosis. (ucl.ac.uk)
- ET-1 further induced connective tissue growth factor (CTGF), as did TGF-β1, however, to lower levels. (wiley.com)
- Connective tissue growth factor (CCN2, also termed CTGF) is one of six structurally related molecules that comprise the CCN family. (bmj.com)
- In mice, connective tissue growth factor (CTGF) is expressed in embryonic β-cells and in adult β-cells during periods of expansion. (diabetesjournals.org)
- CTGF treatment upregulates positive cell-cycle regulators and factors involved in β-cell proliferation, including hepatocyte growth factor, serotonin synthesis, and integrin β1. (diabetesjournals.org)
- The β-cell proliferative factor connective tissue growth factor (CTGF/CCN2) is a member of the CCN family of secreted extracellular matrix-associated proteins ( 7 ). (diabetesjournals.org)
- Depending on the growth factor milieu in the microenvironment, CTGF can regulate several cellular processes including proliferation, adhesion, extracellular matrix remodeling, and angiogenesis ( 12 ). (diabetesjournals.org)
- Recent studies showed that overexpression of CTGF in human oral squamous cell carcinoma reduces cell growth and tumorigenecity. (clinicaltrials.gov)
- Similar tumor growth inhibitory effects were observed in lung cancer cells in which CTGF overexpression was less angiogenic and metastatic due to blocking of the VEGF A signaling pathway. (clinicaltrials.gov)
- CTGF was also reported to be a key regulator of colorectal cancer invasion and metastasis, and it appears to be a better prognostic factor. (clinicaltrials.gov)
- In order to answer these important questions, first, we have performed the preliminary studies to prove CTGF did express in different gastric cancer cell lines including AGS, N87, TSGH, and MKN-45 by using RT-PCR and Western blotting, and gastric cancer tissues by using immunohistochemical method. (clinicaltrials.gov)
- Connective tissue growth factor (CTGF/CCN2) is a member of the CCN family of matricellular proteins. (ovid.com)
- CTGF can bind to several other growth factors modifying their function. (ovid.com)
- CTGF, also known as CCN2 or connective tissue growth factor, is a matricellular protein of the CCN family of extracellular matrix-associated heparin-binding proteins (see also CCN intercellular signaling protein). (wikipedia.org)
- CTGF has important roles in many biological processes, including cell adhesion, migration, proliferation, angiogenesis, skeletal development, and tissue wound repair, and is critically involved in fibrotic disease and several forms of cancers. (wikipedia.org)
- In addition, CTGF also binds growth factors and extracellular matrix proteins. (wikipedia.org)
- It is thought that CTGF can cooperate with TGF-β to induce sustained fibrosis and to exacerbate extracellular matrix production in association other fibrosis-inducing conditions. (wikipedia.org)
- Overexpression of CTGF in fibroblasts promotes fibrosis in the dermis, kidney, and lung, and deletion of Ctgf in fibroblasts and smooth muscle cells greatly reduces bleomycin-induced skin fibrosis. (wikipedia.org)
- In addition to fibrosis, aberrant CTGF expression is also associated with many types of malignancies, diabetic nephropathy and retinopathy, arthritis, and cardiovascular diseases. (wikipedia.org)
- Several clinical trials are now ongoing that investigate the therapeutic value of targeting CTGF in fibrosis, diabetic nephropathy, and pancreatic cancer. (wikipedia.org)
- Background and objectives Connective Tissue Growth Factor (CTGF/CCN-2) is a key player in fibrosis. (asnjournals.org)
- Plasma CTGF levels predict end-stage renal disease and mortality in diabetic chronic kidney disease (CKD), supporting roles in intra- and extrarenal fibrosis. (asnjournals.org)
- Connective-tissue growth factor (CTGF/CCN-2) is a main mediator of fibrogenesis both downstream and independent of transforming growth factor-β1 ( 1 - 3 ). (asnjournals.org)
- CTGF was shown to be a key player in the development and progression of diabetic renal fibrosis. (asnjournals.org)
- In experimental diabetic nephropathy, glomerular and tubulointerstitial CTGF overexpression induces glomerulosclerosis, tubulointerstitial fibrosis, and albuminuria ( 4 - 6 ). (asnjournals.org)
- Likewise, in human diabetic nephropathy, CTGF overexpression in renal biopsies is associated with tubulointerstitial fibrosis, proteinuria, and renal function impairment ( 7 , 8 ), and urinary CTGF levels correlate with albuminuria and renal function impairment ( 9 , 10 ). (asnjournals.org)
- Few data are available, however, on the role of CTGF in nondiabetic chronic kidney disease (CKD), although intra- and extrarenal fibrosis are of well recognized importance in this disease condition ( 16 - 19 ). (asnjournals.org)
- Connective tissue growth factor (CTGF) appears to play a significant role in mediating fibrosis in several tissues. (arvojournals.org)
- Three experiments were performed: (1) CTGF and transforming growth factor (TGF)-β expression were measured quantitatively after GFS, using ELISA. (arvojournals.org)
- 2) After GFS conjunctival bleb tissues were immunostained for the presence of CTGF and TGF-β. (arvojournals.org)
- CTGF and TGF-β were expressed maximally by day 5 after surgery and were both shown to be present in the bleb tissues after GFS. (arvojournals.org)
- Connective tissue growth factor (CTGF) is a secreted peptide that was originally discovered in human umbilical vein endothelial cell conditioned medium and has been implicated in multiple cellular events, including angiogenesis, skeletogenesis, and wound healing. (arvojournals.org)
- 23 24 25 The actions of CTGF have been clearly distinguished from those of TGF-β by showing that CTGF alone does not induce anchorage-independent growth of fibroblasts. (arvojournals.org)
- 27 The mechanisms of CTGF induction involve Smads, Ras/MEK/ERK, protein kinase C, and fibroblast-enriched factors. (arvojournals.org)
- Connective tissue growth factor (CTGF) from basics to clinics. (semanticscholar.org)
- To investigate whether triamcinolone acetonide (TA) affects the expression of vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) in retinal pigment epithelial (RPE) cells exposed to oxidative stress. (arvojournals.org)
- Cellular expression of VEGF, CTGF, and an inducer of both growth factors, transforming growth factor (TGF)-β was investigated with real-time reverse transcription-polymerase chain reaction and Western blot analysis. (arvojournals.org)
- Because VEGF is a major cytokine involved in angiogenesis, and CTGF is a main cytokine related to fibrosis, these results suggest that changes in their expression may be important mechanisms underlying the decreased choroidal neovascularization and fibrosis after administration of TA. (arvojournals.org)
- A gene (connective tissue growth factor [ CTGF ]) is located in that region that encodes a strongly fibrogenic molecule. (pubmedcentralcanada.ca)
- CTGF transcripts are overexpressed in livers affected by fibrosis of various etiologies ( Rachfal and Brigstock, 2003 ). (pubmedcentralcanada.ca)
- Connective tissue growth factor (CTGF) is a secreted protein that is strongly induced in human and experimental heart failure. (mdc-berlin.de)
- To investigate CTGF as a fibrosis inducer, we performed morphological and gene expression analyses of CTGF-TG mice and rat hearts under basal conditions and after stimulation with angiotensin II (Ang II) or isoproterenol, respectively. (mdc-berlin.de)
- In an ischemia/reperfusion model CTGF-TG hearts did not differ from controls.Our data suggest that CTGF itself does not induce cardiac fibrosis. (mdc-berlin.de)
- Cancer Antigen 125 (CA125)levels (indicative of mesothelial cell mass) and connective tissue growth factor (CTGF) levels (a marker of inflammation) will be measured in the spent dialysate to determine whether these markers correlate with cell shedding and apoptosis. (clinicaltrials.gov)
- Heart function, renal hemodynamics, neuroendocrine factors, serum and urine concentration of soluble form connective tissue growth factor (sCTGF), expression of CTGF mRNA, CTGF, α-smooth muscle actin (α-SMA), and low-density lipoprotein receptor-related protein (LRP) in renal tissues were evaluated after 28 days and 60 days of drug administration. (frontiersin.org)
- In vitro experiments were designed to verify the results of in vivo experiments by detecting factors including CTGF, α-SMA in NRK-52E cells. (frontiersin.org)
- Treatment of BXYS was correlated with a restoration of heart function and improvement of renal hemodynamics, lower serum and urine sCTGF, lower CTGF mRNA, CTGF, α-SMA and LRP expression in renal tissues and lower ECM deposition. (frontiersin.org)
- Using liver explants from patients with BA (n = 26), immune-expression of connective tissue growth factor (CTGF), a key fibrogenic cytokine was determined using horseradish-labeled antibodies. (dovepress.com)
- Connective tissue growth factor (CTGF), also known as CCN2, is a member of the CCN family. (thefreelibrary.com)
- For example, high CTGF levels have been associated with tumor growth and adverse prognosis in pancreatic cancer (12) and gastric cancer. (thefreelibrary.com)
- Connective tissue growth factor (CTGF) plays an essential role in the pathogenesis of diabetic nephropathy and we have previously identified that high glucose induced the expression of CTGF by decreasing DNA methylation. (portlandpress.com)
- Immunofluorescence analysis revealed more intense transforming growth factor β2 (TGFβ2) and connective tissue growth factor (CTGF) staining in IVB-treated proliferative diabetic retinopathy (PDR) membranes compared with membranes of patients not receiving IVB therapy. (bmj.com)
- Bevacizumab incubation significantly upregulated TGFβ2 and CTGF in ARPE-19 cells and BV2 microglial cells, but ciliary neurotrophic factor (CNTF) expression was upregulated only in BV2 microglial cells. (bmj.com)
- Conclusions Anti-vascular endothelial growth factor treatment likely accelerates fibrosis in PDR patients via upregulation of TGFβ2, CTGF and CNTF, suggesting the importance of adjunctive therapy for retinal fibrosis. (bmj.com)
- Pamrevlumab is a proprietary, first-in-class, anti-connective tissue growth factor (CTGF) antibody being evaluated in fibrotic disease and cancer. (corporate-ir.net)
- Proteins such as transforming growth factor (TGF), endothelin-1 (ET-1), angiotensin II (Ang II), connective tissue growth factor (CCN2/CTGF), insulin-like growth factor (IGF), and platelet-derived growth factor (PDGF) appear to act in a network that contributes to the development of gingival fibrosis. (hindawi.com)
- This review summarizes recent observations concerning the contribution of TGF- β , CTGF, IGF, PDGF, ET-1, Ang II, and mast cell chymase and tryptase enzymes to fibroblast activation in gingival fibrosis and the potential utility of agents blocking these proteins in affecting the outcome of drug-induced gingival overgrowth. (hindawi.com)
- VEGF upregulates the profibrotic growth factor connective tissue growth factor (CTGF) in various cell types in the newly formed neovascular membranes. (medscape.com)
- Increasing levels of CTGF inactivate VEGF, and when the equilibrium between these two factors shifts to a certain threshold ratio, the neovascular membranes become more fibrotic and less vascular. (medscape.com)
- Fibrosis driven by excess CTGF leads to scarring and blindness. (medscape.com)
- The CCN family presently consists of six members in human also known as: Cyr61 (Cystein rich 61), CTGF (Connective Tissue Growth Factor), Nov (Nephroblastoma Overexpressed gene), WISP-1, 2 and 3 (Wnt-1 Induced Secreted Proteins). (biovendor.com)
- Connective tissue growth factor (CTGF/CCN2) is an extracellular matrix protein composed of four domains which belongs to the CCN protein family. (hindawi.com)
- Connective tissue growth factor (CTGF), a profibrotic cytokine, plays a key role in this deleterious process. (biologists.org)
- At least some of the beneficial effects of mIGF1 transgene expression were due to mIGF1 counteracting the strong increase in CTGF expression within cardiomyocytes caused by SRF deficiency, resulting in the blockade of fibroblast proliferation and related myocardial fibrosis. (biologists.org)
- These findings demonstrate that SRF plays a key role in the modulation of cardiac fibrosis through repression of cardiomyocyte CTGF expression in a paracrine fashion. (biologists.org)
- 3) In chondrocyte culture system, ecogenin/CTGF bound cell surface heparan sulfate proteoglycans after secreted and was then released, suggesting that it is a matricrine factor. (nii.ac.jp)
- These findings suggest that ecogenin/CTGF not only acts as a paracrine and matricrine factor through its specfic receptors but also functions through an alternative intracellular pathway. (nii.ac.jp)
- Publications] Tamatani,T.: 'Establishment of the enzyme-linked immunosorbent assay for connective tissue growth factor (CTGF) and its detection in the sera of biliary atresia'Biochem.Biophys.Res.Commun. (nii.ac.jp)
- Cooper, M. 2004-06-01 00:00:00 Diabetologia (2004) 47:965-968 DOI 10.1007/s00125-004-1423-6 Commentary The time has come to target connective tissue growth factor in diabetic complications Dysregulation of growth factors is amongst the chang- leading to the hypothesis that CTGF contributes to es that occur in cells and tissues in diabetes. (deepdyve.com)
- Indeed, we have recently shown sequently, identifying the key growth factor(s) that that CTGF is also increased in non-renal tissue. (deepdyve.com)
- The cause a particular type and stage of diabetic tissue increases in CTGF correspond with pathological in- damage is of potential importance in preventing and creases in myocardial type III collagen in rodent dia- betic cardiomyopathy . (deepdyve.com)
- In this context, connective tissue growth factor cient mouse model of atheroma, CTGF mRNA and (CTGF), also known as CCN2 , is a prime candi- protein levels are increased in the complex lesions at date. (deepdyve.com)
- Connective tissue growth factor (CTGF), a mediator of TGFβ1/SMAD3-induced fibrosis, was unchanged in hSMAD3-delivered aortas. (biomedcentral.com)
- PCR was performed for vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF) and transforming growth factor-beta (TGF-beta). (biomedsearch.com)
- Connective tissue growth factor (CTGF) plays an important role in the pathogenesis of chronic fibrotic diseases. (biologists.org)
- Lung fibrosis was associated with a marked increase in cells co-expressing epithelial and mesenchymal markers in the lesional and unaffected lung tissue of Col1a2-CTGF mice. (biologists.org)
- Pamrevlumab is a first-in-class antibody developed by FibroGen to inhibit the activity of CTGF, a common factor in fibrotic and proliferative disorders characterized by persistent and excessive scarring that can lead to organ dysfunction and failure. (drugs.com)
- Pamrevlumab is a first-in-class antibody developed by FibroGen that inhibits the activity of connective tissue growth factor (CTGF), a common factor in fibrotic and proliferative disorders. (drugs.com)
- The company applies its pioneering expertise in hypoxia-inducible factor (HIF) and connective tissue growth factor (CTGF) biology to advance innovative medicines to treat unmet needs. (drugs.com)
- Pamrevlumab, an anti-CTGF human monoclonal antibody, is in clinical development for the treatment of idiopathic pulmonary fibrosis (IPF), locally advanced unresectable pancreatic cancer, Duchenne muscular dystrophy (DMD), and coronavirus (COVID-19). (drugs.com)
- SAN FRANCISCO , Sept. 12, 2018 (GLOBE NEWSWIRE) -- FibroGen, Inc. (NASDAQ: FGEN), a biopharmaceutical company, today announced that the U.S. Food and Drug Administration ( FDA ) has granted Fast Track designation for the company's anti-CTGF antibody, pamrevlumab, for the treatment of patients with idiopathic pulmonary fibrosis (IPF). (corporate-ir.net)
- The company applies its pioneering expertise in hypoxia-inducible factor (HIF), connective tissue growth factor (CTGF) biology, and clinical development to advance innovative medicines for the treatment of anemia, fibrotic disease, and cancer. (corporate-ir.net)
- Connective tissue growth factor (CCN2) is a 38 kDa cystein-rich secreted immediate early gene product and is a member of the CCN (Cyr61/CEF-10, CTGF/Fisp-12 and Nov) family of matricellular proteins. (biomedcentral.com)
- 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)
- Connective tissue growth factor (CCN2) is upregulated in pancreatic fibrosis and desmoplastic pancreatic tumours. (bmj.com)
- Connective tissue growth factor(CCN2), a pathogenic factor in diabetic nephropathy. (ovid.com)
- Exosomes mediate intercellular transfer of pro-fibrogenic connective tissue growth factor (CCN2) between hepatic stellate cells, the principal fibrotic cells in the liver. (sigmaaldrich.com)
- Fibrogenic pathways in the liver are principally regulated by hepatic stellate cells (HSC), which produce and respond to fibrotic mediators such as connective tissue growth factor (CCN2). (sigmaaldrich.com)
- Exosomal CCN2 may amplify or fine tune fibrogenic signaling and, in conjunction with other exosome constituents, may have utility as a noninvasive biomarker to assess hepatic fibrosis. (sigmaaldrich.com)
- Connective tissue growth factor (CCN2) is a matricellular preproprotein controlled by proteolytic activation. (uio.no)
- In the present study, we investigated the effects of the red flashing lights exposure on the refraction and axial length of the eyes in vivo and then evaluated their effects on the expression of CCN2 and TGF- β in sclera tissues. (hindawi.com)
- Both CCN2 and TGF- β , as well as p38 MAPK and PI3K, were highly expressed in the sclera tissues exposed to the red flashing light. (hindawi.com)
- CCN2 has been identified to be involved in various cellular functions and biological processes including fibrosis, angiogenesis, differentiation, and wound healing in various cell types [ 4 - 7 ]. (hindawi.com)
- Connective tissue growth factor (CCN2) is upregulated in many fibrotic disorders. (enets.org)
- Increased tumor expression of CCN2 has been shown in patients with small intestinal NETs associated with peritoneal fibrosis. (enets.org)
- Connective tissue growth factor (CCN2) is elevated in many fibrotic disorders. (biomedcentral.com)
- CCN2 may play a role in neuroendocrine tumor-related cardiac fibrosis and may serve as a marker of its earliest stages. (biomedcentral.com)
- Endothelin-1 (ET-1) plays an important role in tissue remodelling and fibrogenesis by inducing synthesis of collagen I via protein kinase C (PKC). (wiley.com)
- Unwinding the collagen fibrils: elucidating the mechanism of pirfenidone and nintedanib in pulmonary fibrosis. (springer.com)
- As the bulk of the skin is largely comprised of connective tissue collagen, the primary molecular features of aged human skin are reduced production of collagen and accumulation of damaged collagen. (novapublishers.com)
- Age-related alterations of dermal connective collagen cause an aberrant tissue microenvironment, which deleteriously influence the risk of developing age-related skin diseases. (novapublishers.com)
- Fibrosis involves activation of fibroblasts, increased production of collagen and fibronectin and transdifferentiation into contractile myofibroblasts. (biochemsoctrans.org)
- At about 7 days growth factors activate fibroblasts to produce type 3 collagen forming a strong scar tissue. (shoulderdoc.co.uk)
- After about 21 days the scar tissue starts to be replaced with normal tissue (type 1 collagen) and the healing process proceeds to completion. (shoulderdoc.co.uk)
- Morphea, also known as localized scleroderma, is a disorder characterized by excessive collagen deposition leading to thickening of the dermis, subcutaneous tissues, or both. (medscape.com)
- Overproduction of collagen, particularly types I and III collagen, by fibroblasts in affected tissues is common to all forms of morphea, although the mechanism by which these fibroblasts are activated is unknown. (medscape.com)
- Proposed factors involved in the pathogenesis of morphea include endothelial cell injury, immunologic (eg, T lymphocyte) and inflammatory activation, and dysregulation of collagen production. (medscape.com)
- These cytokines and growth factors also increase fibroblast proliferation and induce synthesis of excess collagen and connective-tissue growth factor. (medscape.com)
- Once in the vitreous cavity, the RPE cells undergo morphological changes where they attain fibroblastlike activity, secreting growth factors that stimulate collagen and fibronectin production. (medscape.com)
- Extracellular proteins, collagen I or von Willebrand factor are deposited within the microfluidic channel using active perfusion with a pneumatic pump. (jove.com)
- Further studies showed that TAX significantly attenuated left ventricular fibrosis and collagen synthesis through abrogating the phosphorylation of Smad2 and Smad2/3 nuclear translocation. (osti.gov)
- While TGFβ1 is often associated with increased fibrosis, AAV/hSMAD3 delivery exhibited no increase of collagen 1A2 or significantly lower 2A1 expression in the aorta compared with Neo-delivery. (biomedcentral.com)
- Upregulation of distinct collagen transcripts in post-surgery scar tissue: a study of conjunctival fibrosis. (abcam.com)
- Morphea , also known as localized scleroderma , is a thickening and hardening of the skin and subcutaneous tissues from excessive collagen deposition. (wikidoc.org)
- This protection was characterized by decreased lung pathological abnormalities and the fibrotic gene expression of Type I collagen, Type III collagen, α-smooth muscle actin, and connective tissue growth factor. (pubmedcentralcanada.ca)
- These data indicate the importance of phosphorylated ets-2 in the pathogenesis of pulmonary fibrosis through the expression of Type I collagen and (myo)fibroblast activation. (pubmedcentralcanada.ca)
- This study highlights the importance of transcription factor ets-2 in the pathogenesis of pulmonary fibrosis in mice and humans through the regulation of Type I collagen expression. (pubmedcentralcanada.ca)
- 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)
- The EPP and EPS have protective effects against liver fibrosis induced by CCl 4 , and its mechanisms might be associated with their antioxidant activity, the ability of decreasing the level of TGF-β1 and inhibition of collagen synthesis. (biomedcentral.com)
- total collagen content in heart increases and interstitial fibrosis onsets [ 4 ]. (imedpub.com)
- Cyclosporin A induces peritoneal fibrosis and angiogenesis during chronic peritoneal exposure to a glucose-based, lactate-buffered dialysis solution in the rat. (biomedsearch.com)
- CONCLUSION: CsA combined with exposure to dialysis solutions was associated with increased peritoneal fibrosis and angiogenesis. (biomedsearch.com)
- Recent studies had revealed that MALAT1 can play significant roles in the pathophysiological process, tissue inflammation, tumor progression, angiogenesis, cardiovascular remodelling, liver fibrosis, and diabetes progression by modulating gene transcription [ 12 ]. (medsci.org)
- Coincidence of connective tissue growth factor expression with fibrosis and angiogenesis in postoperative peritoneal adhesion formation. (healthtap.com)
- Evidence of epigenetic tags in cardiac fibrosis. (semanticscholar.org)
- Surprisingly, cardiac tissues of both models did not show increased fibrosis or enhanced gene expression of fibrotic markers. (mdc-berlin.de)
- Cardiac fibrosis is critically involved in the adverse remodeling accompanying dilated cardiomyopathies (DCMs), which leads to cardiac dysfunction and heart failure (HF). (biologists.org)
- mIGF1) on disease progression in a mouse model of DCM [cardiac-specific and inducible serum response factor ( SRF ) gene disruption] that mimics some forms of human DCM. (biologists.org)
- They also explain how impaired SRF function observed in human HF promotes fibrosis and adverse cardiac remodeling. (biologists.org)
- 13 More recently, trimetazidine has been suggested to inhibit cardiac fibrosis through an NADPH oxidase-reactive oxygen species-connective tissue growth factor pathway 14 (see figure 1 ). (bmj.com)
- Cardiac hypertrophy is a key pathophysiological component to biomechanical stress, which has been considered to be an independent and predictive risk factor for adverse cardiovascular events. (osti.gov)
- inhibit cardiac hypertrophy and attenuate ventricular fibrosis after pressure overload. (osti.gov)
- Therefore, TAX might be a potential candidate for the treatment of cardiac hypertrophy and fibrosis. (osti.gov)
- Taxifolin inhibited cardiac hypertrophy and attenuated ventricular fibrosis. (osti.gov)
- Cardiovascular Risk Factors and Perioperative Myocardial Infarction , After Non-Cardiac Surgery. (amedeo.com)
- 9,10 Indeed, long-term intravenous infusion of Ang II is associated with the development of hypertension and cardiac fibrosis. (ahajournals.org)
- Cardiac fibrosis is one of the leading causes of heart failure and therapeutic options are limited. (imedpub.com)
- To evaluate its therapeutic potential against cardiac fibrosis, male Wistar rats were injected with isoproterenol (5 mg/ kg) for 8-12 weeks and the aqueous TA extract was administered orally. (imedpub.com)
- Cardiac Fibrosis hardens the ventricles, impeding cardiac contraction-relaxation and separates cardiomyocytes from the extracellular matrix, impairing electrical coupling [ 2 ]. (imedpub.com)
- Fibroblasts are the predominant mediators of cardiac fibrosis, although the mechanistic insights and the therapeutic options are very limited [ 3 ]. (imedpub.com)
- Cardiac fibrosis, the excessive accumulation of extracellular matrix (ECM), remains an unresolved problem in most forms of heart disease. (mdpi.com)
- In order to be successful in preventing, attenuating or reversing cardiac fibrosis, it is essential to understand the processes leading to ECM production and accumulation. (mdpi.com)
- Cardiac fibrosis comes in several forms, i.e., perivascular, interstitial and focal, and this ECM remodeling increases the risk for arrhythmias and may reduce pumping function as in heart failure with reduced ejection fraction (HFrEF). (mdpi.com)
- Cardiac fibrosis is also a main driver of heart failure with preserved ejection fraction (HFpEF) as it increases myocardial stiffness, thereby compromising the distensibility of the ventricles and impairing the filling capacity of the heart [ 10 ]. (mdpi.com)
- There is to date no effective treatment for cardiac fibrosis. (mdpi.com)
- The histopathological hallmark of chronic kidney disease is renal fibrosis, a process of extracellular matrix formation and atrophy of functional renal tissue resulting from sustained injury. (uu.nl)
- The impact of BMP-6 knockdown on renal fibrosis was studied by implementing unilateral ureteral obstruction (UUO) in BMP-6 null and wild-type mice. (uu.nl)
- The data from this study underscore the complexity of interpreting biomarkers for renal fibrosis, especially in complicated settings such as kidney transplantation. (uu.nl)
- Cellular and molecular mechanisms of renal fibrosis. (nih.gov)
- Renal fibrosis, particularly tubulointerstitial fibrosis, is the common final outcome of almost all progressive chronic kidney diseases. (nih.gov)
- Renal fibrosis is also a reliable predictor of prognosis and a major determinant of renal insufficiency. (nih.gov)
- This Review outlines our current understanding of the cellular and molecular mechanisms of renal fibrosis, which could offer novel insights into the development of new therapeutic strategies. (nih.gov)
- Multiple origins of myofibroblasts have been proposed in renal fibrosis. (nih.gov)
- The relative contribution of each source to the myofibroblast pool in renal fibrosis is controversial. (nih.gov)
- Diabetic nephropathy (DN) develops in about 30% of patients with diabetes and is characterized by thickening of renal basement membranes, fibrosis in the glomerulus (glomerulosclerosis), tubular atrophy and interstitial fibrosis, all of which compromise kidney function. (ovid.com)
- Angiotensin II, the main effector of RAS, is a key mediator of renal injury by increasing intraglomerular capillary pressure and ultrafiltration of plasma proteins and by promoting cell growth and fibroproliferative effects. (asnjournals.org)
- Experimental evidence also indicates that aldosterone, besides being a regulator of extracellular fluid volume and sodium and potassium balance, directly contributes to accelerate renal damage by sustaining cell growth, inflammation, and fibrosis. (asnjournals.org)
- Attenuation of growth-promoting and fibroproliferative effect of aldosterone may contribute to protection against progressive renal injury. (asnjournals.org)
- Hypertension and proteinuria are major determinants of renal progression and contribute to glomerulosclerosis, interstitial inflammation, fibrosis, and tubular atrophy, the key morphologic components of progressive scarring of the kidney. (asnjournals.org)
- The renin-angiotensin system (RAS) is centrally involved in this process, and angiotensin II, in particular, has received great consideration as the mediator of renal injury by increasing intraglomerular capillary pressure and ultrafiltration of plasma proteins and by promoting cell growth and fibroproliferative effects. (asnjournals.org)
- increased extracellular matrix (ECM) deposition and fibrosis in renal tissues. (frontiersin.org)
- In conclusion, the current study provided evidences that BXYS played a role in improving heart function and delaying the progress of renal fibrosis. (frontiersin.org)
- This chapter will focus on both the cellular players and the signaling events that contribute to pulmonary fibrosis. (springer.com)
- Multiple stromal populations contribute to pulmonary fibrosis without evidence for epithelial to mesenchymal transition. (springer.com)
- Since then she has established an international track record and is a named inventor on respiratory diagnostic patents in the fields of COPD and Pulmonary Fibrosis. (keele.ac.uk)
- Utilization of ex-vivo cell injury-repair models (incorporating appropriate mechanical stress stimuli) to explore mechanisms in tissue / airway wall remodelling in pulmonary fibrogenesis and rhinovirus-associated airway inflammation. (keele.ac.uk)
- We show that local and transient TGF-β1 overexpression induces homogenous, prolonged, and progressive pleural fibrosis without pleurodesis, associated with severe impairment of pulmonary function. (jimmunol.org)
- We provide evidence that matrix accumulation and fibrosis within the parenchyma evolved through a process involving "mesothelial-fibroblastoid transformation" and suggest that the pleural mesothelial cell may be an important player involved in the development of the subpleural distribution pattern known to be a hallmark of pulmonary fibrosis. (jimmunol.org)
- IPF is a form of progressive pulmonary fibrosis, or abnormal scarring of the lungs. (corporate-ir.net)
- Previous studies highlighted the importance of phosphorylated ets-2 in lung inflammation and extracellular matrix remodeling, two pathways involved in pulmonary fibrosis. (pubmedcentralcanada.ca)
- We hypothesized that phosphorylated ets-2 played an important role in pulmonary fibrosis, and we sought to determine the role of ets-2 in its pathogenesis. (pubmedcentralcanada.ca)
- Ets-2 (A72/A72) mice were protected from bleomycin-induced pulmonary fibrosis, compared with ets-2 (WT/WT) mice. (pubmedcentralcanada.ca)
- Our data present the opportunity for scientists to target ets-2 pharmaceutically for the treatment of pulmonary fibrosis in humans. (pubmedcentralcanada.ca)
- 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)
- Hepatic fibrosis (HF) may develop either slowly or rapidly in schistosome-infected subjects. (pubmedcentralcanada.ca)
- Subjects die from the subsequent effects of hepatic fibrosis (HF). (pubmedcentralcanada.ca)
- Progressive hepatic fibrosis (HF) is a prominent feature of biliary atresia (BA), the most common indication for liver transplantation (LT) in children. (dovepress.com)
- Multiple cellular and molecular events, such as tubular atrophy, microvascular rarefaction and tissue hypoxia, promote scar formation and ensure a vicious progression to end-stage kidney failure. (nih.gov)
- By contrast, EMT could be a late event, and contribute to the irreversible progression of fibrosis. (nih.gov)
- Fibrosis is a pivotal player in heart failure development and progression. (nih.gov)
- Measurements of (markers of) fibrosis in tissue and blood may help to diagnose and risk stratify patients with heart failure, and its treatment may be effective in preventing heart failure and its progression. (nih.gov)
- Significantly, inhibition of either protein can revert the chronic activation of HSCs and impede pathological progression of liver fibrosis in clinically relevant model systems. (frontiersin.org)
- Connective tissue growth factor immunohistochemical expression is associated with gallbladder cancer progression. (thefreelibrary.com)
- 10) Connective tissue growth factor plays an important role in tumor development and cancer progression, and it is found to be expressed in different types of cancer. (thefreelibrary.com)
- Purpose To investigate the progression of epiretinal membranes after intravitreal bevacizumab (IVB) injection therapy in patients with proliferative membranes and evaluate the changes in fibrosis-related cytokines in retinal pigment epithelial cells and glial cells after treatment with bevacizumab. (bmj.com)
- 7 Although IVB therapy provides significant treatment benefits in multiple indications, not all patients achieve an optimal response, as some patients experience the development and progression of tractional retinal detachment, retinal pigment epithelium tearing and accelerate subretinal fibrosis. (bmj.com)
- Time course correlation analysis of biochemical, histochemical and mRNA transcript parameters (=factors) defined 6 clusters for different phases of disease progression. (biomedcentral.com)
- Based on these clusters, we constructed a decision tree of factor combinations potentially useful as markers for different time intervals of disease progression. (biomedcentral.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)
Liver fibrosis induced by carbon tetrachloride2
- 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)
Tubular atrophy and interstitial fibrosis2
- Nevertheless, patients at higher risk for tubular atrophy and interstitial fibrosis (TA/IF) development should be carefully monitored for tubular function as well as glomerular performance. (scielo.br)
- Long-term kidney allograft survival is reduced by the unavoidable occurrence of tissue fibrosis, namely, glomerulosclerosis, tubular atrophy and interstitial fibrosis (TA/IF). (scielo.br)
- 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)
- By in situ hybridization and immunohistochemistry, the respective mRNA moieties and proteins were localized in the tissue samples. (nih.gov)
- Tissue repair begins with the deposit of extracellular matrix proteins (ECMPs) in the damaged tissues, which are later replaced by normal hepatocytes. (pubmedcentralcanada.ca)
- In this paper, we examine the evidence for a role of IGFBP-5 in fibrosis and highlight its structural relationship with other matrix proteins and growth factors also implicated in tissue remodelling. (biochemsoctrans.org)
- It belongs to a large family of cytokines called the Transforming growth factor beta superfamily , which includes the TGF-β family , Bone morphogenetic proteins (BMPs), growth and differentiation factors (GDFs), inhibins and activins . (wikipedia.org)
- Taking into consideration the physiological events that occur during development of graft fibrosis, we have proposed that early detection of proximal tubular cell dysfunction by urinary measurement of small proteins may offer a reliable and sensitive means of predicting long-term graft function. (scielo.br)
- Connective Tissue Growth Factor belongs to the CCN family of proteins. (biovendor.com)
- The full-length protein consists of four modules: - Module I shares partial identity with the N-terminal part of the Insulin-like Growth Factor Binding Proteins (IGFBPs). (biovendor.com)
- These downstream genes would then code for intracellular proteins, usually transcription factors, and have a more limited effect than a systemically secreted protein. (biomedcentral.com)
- This injury results in increased levels of adhesion molecules (circulating intercellular adhesion molecule-1, vascular cell adhesion molecule 1, and E-selectin) and fibrogenic T-helper 2 cytokines such as interleukin (IL)-4, IL-6, and transforming growth factor-beta (TGF-beta). (medscape.com)
- Collectively, these hormones and cytokines result in the activation of gingival fibroblasts cells within connective tissue. (hindawi.com)
- 21 In addition, chronic hyperinsulinemia promotes de novo hepatic lipogenesis through upregulation of lipogenic transcription factors 21 , 22 , 23 and may activate profibrotic cytokines such as connective tissue growth factor. (cmaj.ca)
- 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)
Role in the pathogenesis2
- Since inflammation is the prerequisite for gingival overgrowth, mast cells and its protease enzymes also play a vital role in the pathogenesis of gingival fibrosis. (hindawi.com)
- Evidence suggests that genetic factors also might have a significant role in the pathogenesis of drug-induced gingival overgrowth and in the patient's susceptibility to this unwanted effect. (hindawi.com)
- 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)
- There was also increased tubulointerstitial damage and an altered, profibrotic growth factor profile. (uu.nl)
- Rise in antifibrotic and decrease in profibrotic microRNA protect the heart against fibrosis during pregnancy: A preliminary study. (semanticscholar.org)
- Connective-tissue growth factor is a soluble mediator that enhances and perpetuates the profibrotic effects of TGF-beta. (medscape.com)
- 1 Vascular endothelial growth factor (VEGF) is a key factor in the pathogenesis of intraocular vascular diseases. (bmj.com)
- The pathogenesis of insulin resistance is complex and is likely to involve many genetic polymorphisms that influence insulin secretion and action as well as environmental factors that promote obesity and immobility. (cmaj.ca)
- The pathogenesis of liver fibrosis remains elusive. (biomedcentral.com)
- TGF-β3 also plays an essential role in controlling the development of lungs in mammals, by also regulating cell adhesion and ECM formation in this tissue, and controls wound healing by regulating the movements of epidermal and dermal cells in injured skin. (wikipedia.org)
- In general, PDGF isoforms are potent mitogens for connective tissue cells, including dermal fibroblasts, glial cells, arterial smooth muscle cells and some epithelial and endothelial cells. (rndsystems.com)
- 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)
- However, chronic liver damage leads to perpetual HSC activation, progressive formation of pathological scar tissue and ultimately, cirrhosis and organ failure. (frontiersin.org)
- The histologic spectrum of NAFLD spans from generally benign, bland steatosis to steatosis with evidence of hepatocellular inflammation and damage (nonalcoholic steatohepatitis, or NASH), which may be complicated by progressive fibrosis and cirrhosis. (cmaj.ca)
- Advanced liver fibrosis could leads to cirrhosis and liver failure eventually. (biomedcentral.com)
- Disrupted bile secretion leads to liver damage characterized by inflammation, fibrosis, eventually cirrhosis, and hepatocellular cancer. (biomedcentral.com)
- Progressive retinal ischemia leads to secretion of growth factors, especially vascular endothelial growth factor (VEGF). (medscape.com)
- During adulthood, they are implicated in wound healing, bone fracture repair, and pathologies such as: fibrosis, vascular ailments and tumourigenesis. (biovendor.com)
- In contrast, hyperoxic conditions induced the dwon-regulation of vascular endothelial growth factor and hepatocyte growth factor. (nih.gov)
- 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)
- 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)
Inflammation and fibrosis1
Injury and fibrosis1
- 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)