Regulation of PDGF and its receptors in fibrotic diseases.

Platelet-derived growth factor (PDGF) isoforms play a major role in stimulating the replication, survival, and migration of myofibroblasts during the pathogenesis of fibrotic diseases. During fibrogenesis, PDGF is secreted by a variety of cell types as a response to injury, and many pro-inflammatory cytokines mediate their mitogenic effects via the autocrine release of PDGF. PDGF action is determined by the relative expression of PDGF alpha-receptors (PDGFRalpha) and beta-receptors (PDGFRbeta) on the surface of myofibroblasts. These receptors are induced during fibrogenesis, thereby amplifying biological responses to PDGF isoforms. PDGF action is also modulated by extracellular binding proteins and matrix molecules. This review summarizes the literature on the role of PDGF and its receptors in the development of fibrosis in a variety of organ systems, including lung, liver, kidney, and skin.

[1]  A. Brody,et al.  Cytokine-binding proteins in the lung. , 1995, The American journal of physiology.

[2]  Álvaro R. Osornio-Vargas,et al.  Interleukin 1 beta (IL-1 beta) and the IL-1 beta-alpha 2-macroglobulin complex upregulate the platelet-derived growth factor alpha-receptor on rat pulmonary fibroblasts. , 1995, American journal of respiratory cell and molecular biology.

[3]  Slomowitz La.  Progression of renal disease. , 1988 .

[4]  D. Morgan,et al.  Susceptibility of cyclooxygenase-2-deficient mice to pulmonary fibrogenesis. , 2002, The American journal of pathology.

[5]  A. Brody,et al.  Interferon-gamma modulates lung macrophage production of PDGF-BB and fibroblast growth. , 1996, Journal of lipid mediators and cell signalling.

[6]  O. Haas,et al.  Treatment of chronic myelogenous leukemia with the tyrosine kinase inhibitor STI571 results in marked regression of bone marrow fibrosis. , 2002, Blood.

[7]  H. Abboud,et al.  Effect of platelet-derived growth factor isoforms in rat metanephric mesenchymal cells. , 2002, American journal of physiology. Renal physiology.

[8]  I. Homma,et al.  Activated protein C inhibits the expression of platelet-derived growth factor in the lung. , 2003, American journal of respiratory and critical care medicine.

[9]  C. Betsholtz,et al.  Abnormal gastrointestinal development in PDGF-A and PDGFR-(alpha) deficient mice implicates a novel mesenchymal structure with putative instructive properties in villus morphogenesis. , 2000, Development.

[10]  S. Friedman,et al.  Hepatic fibrosis. Pathogenesis and principles of therapy , 2001 .

[11]  S. Pizzo,et al.  Oxidized alpha2-macroglobulin (alpha2M) differentially regulates receptor binding by cytokines/growth factors: implications for tissue injury and repair mechanisms in inflammation. , 1998, Journal of immunology.

[12]  E. Baldi,et al.  Cell adhesion regulates platelet‐derived growth factor–induced MAP kinase and PI‐3 kinase activation in stellate cells , 2002, Hepatology.

[13]  David A. Lynch,et al.  Idiopathic pulmonary fibrosis: Diagnosis and treatment: International Consensus Statement , 2000 .

[14]  H. Herbst,et al.  Expression of platelet-derived growth factor and its receptors in normal human liver and during active hepatic fibrogenesis. , 1996, The American journal of pathology.

[15]  N. Janjić,et al.  Novel approach to specific growth factor inhibition in vivo: antagonism of platelet-derived growth factor in glomerulonephritis by aptamers. , 1999, The American journal of pathology.

[16]  L. Truong,et al.  J Am Soc Nephrol 14: 2544–2555, 2003 Obstructive Uropathy in Mice and Humans: Potential Role for PDGF-D in the Progression of Tubulointerstitial Injury , 2022 .

[17]  B. Wallaert,et al.  Mechanisms of fibrosis in coal workers' pneumoconiosis. Increased production of platelet-derived growth factor, insulin-like growth factor type I, and transforming growth factor beta and relationship to disease severity. , 1994, American journal of respiratory and critical care medicine.

[18]  C. Alpers,et al.  Demonstration of PDGF B-chain mRNA in glomeruli in mesangial proliferative nephritis by in situ hybridization. , 1991, Kidney international.

[19]  A. Haverich,et al.  Gene expression of profibrotic mediators in bronchiolitis obliterans syndrome after lung transplantation. , 1998, Scandinavian cardiovascular journal : SCJ.

[20]  J. Lasky,et al.  Reversible binding of platelet-derived growth factor-AA, -AB, and -BB isoforms to a similar site on the "slow" and "fast" conformations of alpha 2-macroglobulin. , 1992, The Journal of biological chemistry.

[21]  O. Katoh,et al.  Platelet derived growth factor messenger RNA is increased in bone marrow megakaryocytes in patients with myeloproliferative disorders , 1990, American journal of hematology.

[22]  C. Heldin,et al.  New members of the platelet-derived growth factor family of mitogens. , 2002, Archives of biochemistry and biophysics.

[23]  J. Pfeilschifter,et al.  Platelet-derived growth factor and fibroblast growth factor differentially regulate interleukin 1beta- and cAMP-induced nitric oxide synthase expression in rat renal mesangial cells. , 1997, The Journal of clinical investigation.

[24]  C. S. Gal,et al.  Growth inhibitory properties of endothelin-1 in human hepatic myofibroblastic Ito cells. An endothelin B receptor-mediated pathway. , 1995, The Journal of clinical investigation.

[25]  H. Herbst,et al.  Phosphatidylinositol 3-kinase is required for platelet-derived growth factor's actions on hepatic stellate cells. , 1997, Gastroenterology.

[26]  L. Klareskog,et al.  Increased expression of platelet-derived growth factor type B receptors in the skin of patients with systemic sclerosis. , 1990, Arthritis and rheumatism.

[27]  Gary R. Grotendorst,et al.  Exaggerated spontaneous release of platelet-derived growth factor by alveolar macrophages from patients with idiopathic pulmonary fibrosis. , 1987, The New England journal of medicine.

[28]  J. Bonner,et al.  Regulation of Interleukin-1β-induced Platelet-derived Growth Factor Receptor-α Expression in Rat Pulmonary Myofibroblasts by p38 Mitogen-activated Protein Kinase* , 2000, The Journal of Biological Chemistry.

[29]  S. L. Gonias,et al.  Identical or overlapping sequences in the primary structure of human alpha(2)-macroglobulin are responsible for the binding of nerve growth factor-beta, platelet-derived growth factor-BB, and transforming growth factor-beta. , 2000, The Journal of biological chemistry.

[30]  A. Brody,et al.  Differential proliferation of rat lung fibroblasts induced by the platelet-derived growth factor-AA, -AB, and -BB isoforms secreted by rat alveolar macrophages. , 1991, American journal of respiratory cell and molecular biology.

[31]  A. Gentilini,et al.  The mitogenic effect of platelet-derived growth factor in human hepatic stellate cells requires calcium influx. , 1995, The American journal of physiology.

[32]  R. Brekken,et al.  SPARC, a matricellular protein: at the crossroads of cell-matrix communication. , 2001, Matrix biology : journal of the International Society for Matrix Biology.

[33]  J. N. Evans,et al.  Increased expression of PDGF-B (c-sis) mRNA in rat lung precedes DNA synthesis and tissue repair during chronic hyperoxia. , 1989, American journal of respiratory cell and molecular biology.

[34]  A. Rosen,et al.  Autoimmunity in scleroderma: the origin, pathogenetic role, and clinical significance of autoantibodies , 2003, Current opinion in rheumatology.

[35]  F. Ridolfi,et al.  Effect of pirfenidone on rat hepatic stellate cell proliferation and collagen production. , 2002, Journal of hepatology.

[36]  T. Okura,et al.  Transcriptional regulation of the platelet-derived growth factor alpha receptor gene via CCAAT/enhancer-binding protein-delta in vascular smooth muscle cells. , 1999, The Journal of biological chemistry.

[37]  A B West,et al.  Myofibroblasts. II. Intestinal subepithelial myofibroblasts. , 1999, American journal of physiology. Cell physiology.

[38]  M. Kraft,et al.  IL-4, IL-13, and dexamethasone augment fibroblast proliferation in asthma. , 2001, The Journal of allergy and clinical immunology.

[39]  K. Shirato,et al.  Platelet-derived growth factor, basic fibroblast growth factor, and interferon gamma increase type IV collagen production in human fetal mesangial cells via a transforming growth factor-beta-dependent mechanism. , 2000, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[40]  E. Krebs,et al.  Protein kinase A antagonizes platelet-derived growth factor-induced signaling by mitogen-activated protein kinase in human arterial smooth muscle cells. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[41]  K. Inoki,et al.  Regulation of rat mesangial cell migration by platelet-derived growth factor, angiotensin II, and adrenomedullin. , 1999, Journal of the American Society of Nephrology : JASN.

[42]  R. Gay,et al.  Immunohistologic demonstration of platelet-derived growth factor (PDGF) and sis-oncogene expression in scleroderma. , 1989, The Journal of investigative dermatology.

[43]  A. Brody,et al.  Interferon-γ modulates lung macrophage production of PDGF-BB and fibroblast growth , 1996 .

[44]  Gary R. Grotendorst,et al.  Activated human monocytes express the c-sis proto-oncogene and release a mediator showing PDGF-like activity , 1986, Nature.

[45]  D M Bissell,et al.  Cell-specific expression of transforming growth factor-beta in rat liver. Evidence for autocrine regulation of hepatocyte proliferation. , 1995, The Journal of clinical investigation.

[46]  D. Morgan,et al.  Specific inhibitors of platelet-derived growth factor or epidermal growth factor receptor tyrosine kinase reduce pulmonary fibrosis in rats. , 1999, The American journal of pathology.

[47]  G. Gurujeyalakshmi,et al.  Pirfenidone inhibits PDGF isoforms in bleomycin hamster model of lung fibrosis at the translational level. , 1999, American journal of physiology. Lung cellular and molecular physiology.

[48]  A. Brody,et al.  Platelet-derived growth factor (PDGF)-AA, -AB, and -BB induce differential chemotaxis of early-passage rat lung fibroblasts in vitro. , 1995, American journal of respiratory cell and molecular biology.

[49]  L. Ostrowski,et al.  Chrysotile asbestos stimulates platelet-derived growth factor-AA production by rat lung fibroblasts in vitro: evidence for an autocrine loop. , 1995, American Journal of Respiratory Cell and Molecular Biology.

[50]  J. Pablos,et al.  Decreased susceptibility to Fas-induced apoptosis of systemic sclerosis dermal fibroblasts. , 2001, Arthritis and rheumatism.

[51]  V. Petkov,et al.  A preliminary study of long-term treatment with interferon gamma-1b and low-dose prednisolone in patients with idiopathic pulmonary fibrosis. , 1999, The New England journal of medicine.

[52]  J. Lasky,et al.  Rapid activation of PDGF-A and -B expression at sites of lung injury in asbestos-exposed rats. , 1997, American journal of respiratory cell and molecular biology.

[53]  H. Abboud,et al.  Interferon-gamma-mediated activation of STAT1alpha regulates growth factor-induced mitogenesis. , 1996, The Journal of clinical investigation.

[54]  R. Silver,et al.  Scleroderma bronchoalveolar lavage fluid contains thrombin, a mediator of human lung fibroblast proliferation via induction of platelet-derived growth factor alpha-receptor. , 1994, American journal of respiratory cell and molecular biology.

[55]  J. Bonner,et al.  p38 mitogen-activated protein kinase regulates growth factor-induced mitogenesis of rat pulmonary myofibroblasts. , 2002, American journal of respiratory cell and molecular biology.

[56]  J. Kelley,et al.  Variable expression of platelet-derived growth factor family proteins in acute lung injury. , 1993, American journal of respiratory cell and molecular biology.

[57]  J. White,et al.  Pathogenesis of pulmonary fibrosis: platelet-derived growth factor precedes structural alterations in the Hermansky-Pudlak syndrome. , 1994, The Journal of laboratory and clinical medicine.

[58]  A. Mallat,et al.  Platelet-derived Growth Factor-BB and Thrombin Generate Positive and Negative Signals for Human Hepatic Stellate Cell Proliferation , 1998, The Journal of Biological Chemistry.

[59]  M. Hansmann,et al.  Detection and quantification of transforming growth factor beta (TGF-beta) and platelet-derived growth factor (PDGF) release by normal human megakaryocytes. , 1995, Leukemia.

[60]  F. Marra,et al.  Cytokine Receptors and Signaling in Hepatic Stellate Cells , 2001, Seminars in liver disease.

[61]  S. Dower,et al.  Interleukin-1 mitogenic activity for fibroblasts and smooth muscle cells is due to PDGF-AA. , 1989, Science.

[62]  I. Rosas,et al.  Induction of the lung myofibroblast PDGF receptor system by urban ambient particles from Mexico City. , 1998, American journal of respiratory cell and molecular biology.

[63]  M. Kawakami,et al.  Enhanced Expression of Platelet-Derived Growth Factor-β Receptor by High Glucose Involvement of Platelet-Derived Growth Factor in Diabetic Angiopathy , 1996, Diabetes.

[64]  K. Yamamura,et al.  Chronic active hepatitis in transgenic mice expressing interferon-gamma in the liver. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[65]  S. Friedman,et al.  Activation of cultured rat hepatic lipocytes by Kupffer cell conditioned medium. Direct enhancement of matrix synthesis and stimulation of cell proliferation via induction of platelet-derived growth factor receptors. , 1989, The Journal of clinical investigation.

[66]  M. Trojanowska,et al.  Selective upregulation of platelet-derived growth factor alpha receptors by transforming growth factor beta in scleroderma fibroblasts , 1992, The Journal of experimental medicine.

[67]  D. Schuppan,et al.  Type I, II, III, IV, V, and VI Collagens Serve as Extracellular Ligands for the Isoforms of Platelet-derived Growth Factor (AA, BB, and AB)* , 1996, The Journal of Biological Chemistry.

[68]  A. Simm,et al.  Mitogenic effect of PDGF-AA on cardiac fibroblasts , 1998, Basic Research in Cardiology.

[69]  A. Phillips,et al.  Elevated D-glucose concentrations modulate TGF-beta 1 synthesis by human cultured renal proximal tubular cells. The permissive role of platelet-derived growth factor. , 1995, The American journal of pathology.

[70]  A. Brody,et al.  Rat alveolar macrophage-derived platelet-derived growth factor is chemotactic for rat lung fibroblasts. , 1990, American journal of respiratory cell and molecular biology.

[71]  G. Rodnan,et al.  Increased collagen accumulation in dermal fibroblast cultures from patients with progressive systemic sclerosis (scleroderma). , 1978, The Journal of laboratory and clinical medicine.

[72]  D. Madtes,et al.  Interleukin-13 stimulates the proliferation of lung myofibroblasts via a signal transducer and activator of transcription-6-dependent mechanism: a possible mechanism for the development of airway fibrosis in asthma. , 2003, Chest.

[73]  B. Keyt,et al.  A fully human monoclonal antibody (CR002) identifies PDGF-D as a novel mediator of mesangioproliferative glomerulonephritis. , 2003, Journal of the American Society of Nephrology : JASN.

[74]  J. Lasky,et al.  Upregulation of the PDGF-alpha receptor precedes asbestos-induced lung fibrosis in rats. , 1998, American journal of respiratory and critical care medicine.

[75]  H. Ihn,et al.  Growth regulation in scleroderma fibroblasts: increased response to transforming growth factor-beta 1. , 1995, The Journal of investigative dermatology.

[76]  B. Cochran,et al.  Activation of the JAK-STAT pathway by reactive oxygen species. , 1998, American journal of physiology. Cell physiology.

[77]  D. Powell.  Intestinal subepithelial myofibroblasts , 1999 .

[78]  G. Dubyak,et al.  Mitogenic signals for platelet-derived growth factor isoforms in liver fat-storing cells. , 1991, The American journal of physiology.

[79]  A. Brody,et al.  Alpha-macroglobulin secreted by alveolar macrophages serves as a binding protein for a macrophage-derived homologue of platelet-derived growth factor. , 1989, American journal of respiratory cell and molecular biology.

[80]  L. Wakefield,et al.  Independent regulation of transforming growth factor-beta1 transcription and translation by glucose and platelet-derived growth factor. , 2002, The American journal of pathology.

[81]  D. Morgan,et al.  Induction of PDGF receptor-alpha in rat myofibroblasts during pulmonary fibrogenesis in vivo. , 1998, The American journal of physiology.

[82]  L. Gesualdo,et al.  Effects of platelet-derived growth factor and other polypeptide mitogens on DNA synthesis and growth of cultured rat liver fat-storing cells. , 1989, The Journal of clinical investigation.

[83]  R. Ross,et al.  A significant part of macrophage-derived growth factor consists of at least two forms of PDGF , 1985, Cell.

[84]  S. Friedman,et al.  Liver fibrosis -- from bench to bedside. , 2003, Journal of hepatology.

[85]  Álvaro R. Osornio-Vargas,et al.  Lipopolysaccharide up-regulates platelet-derived growth factor (PDGF) alpha-receptor expression in rat lung myofibroblasts and enhances response to all PDGF isoforms. , 1996, Journal of immunology.

[86]  M. Kitagawa,et al.  Immunolocalization of platelet-derived growth factor, transforming growth factor-beta, and fibronectin in acute megakaryoblastic leukemia manifesting tumor formation. , 1994, Human pathology.

[87]  S. Sebti,et al.  Tyrosine phosphorylation of focal adhesion kinase by PDGF is dependent on Ras in human hepatic stellate cells , 2000, Hepatology.

[88]  M. Pinzani.  PDGF and signal transduction in hepatic stellate cells. , 2002, Frontiers in bioscience : a journal and virtual library.

[89]  J. Hollander.  ARTHRITIS AND ALLIED CONDITIONS , 1949 .

[90]  H. Abboud.  Role of platelet-derived growth factor in renal injury. , 1995, Annual review of physiology.

[91]  D. Lacey,et al.  Platelet-derived growth factor-BB induces renal tubulointerstitial myofibroblast formation and tubulointerstitial fibrosis. , 1996, The American journal of pathology.

[92]  A. Migliaccio,et al.  Development of myelofibrosis in mice genetically impaired for GATA-1 expression (GATA-1(low) mice). , 2002, Blood.

[93]  Philippe Soriano,et al.  Abnormal kidney development and hematological disorders in PDGF beta-receptor mutant mice. , 1994, Genes & development.

[94]  R. Shaw,et al.  Dexamethasone-induced increase in platelet-derived growth factor (B) mRNA in human alveolar macrophages and myelomonocytic HL60 macrophage-like cells. , 1992, American journal of respiratory cell and molecular biology.

[95]  H. Liapis,et al.  Increased expression of platelet-derived growth factor A and collagenous matrix proteins in congenital multicystic renal dysplasia. , 1997, Nephron.

[96]  J. Pouysségur,et al.  Mitogen-activated protein kinases p42mapk and p44mapk are required for fibroblast proliferation. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[97]  D. Morgan,et al.  Alveolar macrophages stimulated with titanium dioxide, chrysotile asbestos, and residual oil fly ash upregulate the PDGF receptor-alpha on lung fibroblasts through an IL-1beta-dependent mechanism. , 1997, American journal of respiratory cell and molecular biology.

[98]  C. Alpers,et al.  Developmental patterns of PDGF B-chain, PDGF-receptor, and alpha-actin expression in human glomerulogenesis. , 1992, Kidney international.

[99]  A. Chott,et al.  Ineffectiveness of interferon-gamma in the treatment of idiopathic myelofibrosis: a pilot study. , 2001, Annals of hematology.

[100]  R. Nakhleh,et al.  Obliterative bronchiolitis after lung transplantation: a fibroproliferative disorder associated with platelet-derived growth factor. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[101]  T. Wright,et al.  Endogenous IL-1α from systemic sclerosis fibroblasts induces IL-6 and PDGF-A , 1999 .

[102]  J. Bonner,et al.  Inhibition of Platelet-derived Growth Factor-BB-induced Fibroblast Proliferation by Plasmin-activated -Macroglobulin Is Mediated via an -Macroglobulin Receptor/Low Density Lipoprotein Receptor-related Protein-dependent Mechanism (*) , 1995, The Journal of Biological Chemistry.

[103]  N. Martinet,et al.  Presence of platelet-derived growth factor in normal and fibrotic lung is specifically associated with interstitial macrophages, while both interstitial macrophages and alveolar epithelial cells express the c-sis proto-oncogene. , 1991, American journal of respiratory cell and molecular biology.

[104]  M. Reed,et al.  SPARC is expressed in renal interstitial fibrosis and in renal vascular injury. , 1996, Kidney international.

[105]  M. Selman,et al.  Platelet-derived growth factor in idiopathic pulmonary fibrosis. , 1990, The Journal of clinical investigation.

[106]  M. Reed,et al.  SPARC is expressed by mesangial cells in experimental mesangial proliferative nephritis and inhibits platelet-derived-growth-factor-medicated mesangial cell proliferation in vitro. , 1996, The American journal of pathology.

[107]  K Seyama,et al.  Localization of platelet-derived growth factor and insulin-like growth factor I in the fibrotic lung. , 1995, American journal of respiratory and critical care medicine.

[108]  J. Reilly.  3 Pathogenesis and management of idiopathic myelofibrosis , 1998 .

[109]  C. Betsholtz,et al.  PDGF-A Signaling Is a Critical Event in Lung Alveolar Myofibroblast Development and Alveogenesis , 1996, Cell.

[110]  J. Bonner,et al.  Maximal PDGF-induced lung fibroblast chemotaxis requires PDGF receptor-alpha. , 1996, The American journal of physiology.

[111]  F. Eitner,et al.  Expression of a novel PDGF isoform, PDGF-C, in normal and diseased rat kidney. , 2002, Journal of the American Society of Nephrology : JASN.

[112]  E. Taskinen,et al.  Chronic allograft nephropathy is prevented by inhibition of platelet-derived growth factor receptor: tyrosine kinase inhibitors as a potential therapy , 2003, Transplantation.

[113]  R. Gilbert,et al.  Over-expression of platelet-derived growth factor in human diabetic nephropathy. , 2003, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[114]  R. Clark,et al.  Pathogenesis of pulmonary fibrosis in interstitial lung disease. Alveolar macrophage PDGF(B) gene activation and up-regulation by interferon gamma. , 1991, The American review of respiratory disease.

[115]  Álvaro R. Osornio-Vargas,et al.  Transforming growth factor beta 1 downregulates the platelet-derived growth factor alpha-receptor subtype on human lung fibroblasts in vitro. , 1995, American journal of respiratory cell and molecular biology.

[116]  Y. Kaneda,et al.  A histologically distinctive interstitial pneumonia induced by overexpression of the interleukin 6, transforming growth factor beta 1, or platelet-derived growth factor B gene. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[117]  N. Janjić,et al.  Specific antagonism of PDGF prevents renal scarring in experimental glomerulonephritis. , 2001, Journal of the American Society of Nephrology : JASN.

[118]  T. Wright,et al.  Endogenous IL-1alpha from systemic sclerosis fibroblasts induces IL-6 and PDGF-A. , 1999, The Journal of clinical investigation.

[119]  J. Bonner,et al.  Role of Nuclear Factor-κB and Mitogen-Activated Protein Kinase Signaling Pathways in IL-1β-Mediated Induction of α-PDGF Receptor Expression in Rat Pulmonary Myofibroblasts , 1998, The Journal of Immunology.

[120]  A Kahn,et al.  Interstitial lung disease. , 1982, The Journal of the Arkansas Medical Society.

[121]  T. Okura,et al.  Transcriptional Regulation of the Platelet-derived Growth Factor α Receptor Gene via CCAAT/Enhancer-binding Protein-δ in Vascular Smooth Muscle Cells* , 1999, The Journal of Biological Chemistry.

[122]  Richard M. Ransohoff,et al.  Stat1-independent regulation of gene expression in response to IFN-γ , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[123]  A. Chott,et al.  Ineffectiveness of interferon-γ in the treatment of idiopathic myelofibrosis: a pilot study , 2001, Annals of Hematology.

[124]  E. CARwni LEROYwith,et al.  Increased Collagen Synthesis by Scleroderma Skin Fibroblasts In Vitro A POSSIBLE DEFECT IN THE REGULATION OR ACTIVATION OF THE SCLERODERMA FIBROBLAST , 2022 .

[125]  T. Sjöblom,et al.  Transgenic overexpression of platelet-derived growth factor-C in the mouse heart induces cardiac fibrosis, hypertrophy, and dilated cardiomyopathy. , 2003, The American journal of pathology.

[126]  C. Heldin,et al.  PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor. , 2001, Nature cell biology.

[127]  M. Donati,et al.  Increased Plasma Levels of Platelet-Derived Growth Factor Activity in Patients with Progressive Systemic Sclerosis , 1989, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[128]  S. L. Gonias,et al.  Identical or Overlapping Sequences in the Primary Structure of Human α2-Macroglobulin Are Responsible for the Binding of Nerve Growth Factor-β, Platelet-derived Growth Factor-BB, and Transforming Growth Factor-β* , 2000, The Journal of Biological Chemistry.

[129]  M. Sleigh,et al.  Accumulation of PDGF B and cell-binding forms of PDGF A in the extracellular matrix , 1993, The Journal of cell biology.

[130]  S. Akiba,et al.  ERK and p38 MAP kinase are involved in arachidonic acid release induced by H(2)O(2) and PDGF in mesangial cells. , 2002, American journal of physiology. Renal physiology.

[131]  V. Paradis,et al.  Effects and Regulation of Connective Tissue Growth Factor on Hepatic Stellate Cells , 2002, Laboratory Investigation.

[132]  S. Klahr,et al.  Progression of renal disease. , 1988, Seminars in nephrology.

[133]  S. Friedman,et al.  Induction of beta-platelet-derived growth factor receptor in rat hepatic lipocytes during cellular activation in vivo and in culture. , 1994, The Journal of clinical investigation.

[134]  W. Richardson,et al.  The alternative-splice isoforms of the PDGF A-chain differ in their ability to associate with the extracellular matrix and to bind heparin in vitro. , 1992, Growth factors.

[135]  C. Alpers,et al.  Infusion of platelet-derived growth factor or basic fibroblast growth factor induces selective glomerular mesangial cell proliferation and matrix accumulation in rats. , 1993, The Journal of clinical investigation.

[136]  H. Abboud,et al.  Activation of PLC and PI 3 kinase by PDGF receptor alpha is not sufficient for mitogenesis and migration in mesangial cells. , 2000, Kidney international.

[137]  J. Korn,et al.  Role of apoptosis and transforming growth factor beta1 in fibroblast selection and activation in systemic sclerosis. , 2000, Arthritis and rheumatism.

[138]  P. Goldschmidt-Clermont,et al.  Deficient Smad7 expression: A putative molecular defect in scleroderma , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[139]  S. Friedman.  Molecular Regulation of Hepatic Fibrosis, an Integrated Cellular Response to Tissue Injury* , 2000, The Journal of Biological Chemistry.

[140]  Álvaro R. Osornio-Vargas,et al.  Differential Binding and Regulation of Platelet-derived Growth Factor A and B Chain Isoforms by α2-Macroglobulin (*) , 1995, The Journal of Biological Chemistry.

[141]  A. Gentilini,et al.  Inhibition by pentoxifylline of extracellular signal‐regulated kinase activation by platelet‐derived growth factor in hepatic stellate cells , 1996, British journal of pharmacology.

[142]  Y. Kawaguchi.  IL‐lα gene expression and protein production by fibroblasts from patients with systemic sclerosis , 1994, Clinical and experimental immunology.

[143]  Rey-Huei Chen,et al.  Molecular interpretation of ERK signal duration by immediate early gene products , 2002, Nature Cell Biology.

[144]  R. Crystal,et al.  Upregulation of platelet-derived growth factor-A and -B gene expression in alveolar macrophages of individuals with idiopathic pulmonary fibrosis. , 1990, The Journal of clinical investigation.

[145]  C. Alpers,et al.  Visceral glomerular epithelial cells can proliferate in vivo and synthesize platelet-derived growth factor B-chain. , 1993, The American journal of pathology.

[146]  D. Fabbro,et al.  Platelet-derived growth factor and angiotensin II stimulate the mitogen-activated protein kinase cascade in renal mesangial cells: comparison of hypertrophic and hyperplastic agonists. , 1995, The Biochemical journal.

[147]  C. Strange,et al.  Elevated levels of platelet derived growth factor and transforming growth factor-beta 1 in bronchoalveolar lavage fluid from patients with scleroderma. , 1995, The Journal of rheumatology.

[148]  J. Lasky,et al.  Emphysematous lesions, inflammation, and fibrosis in the lungs of transgenic mice overexpressing platelet-derived growth factor. , 1999, The American journal of pathology.

[149]  David A. Brenner,et al.  The Role of Focal Adhesion Kinase-Phosphatidylinositol 3-Kinase-Akt Signaling in Hepatic Stellate Cell Proliferation and Type I Collagen Expression* , 2003, The Journal of Biological Chemistry.

[150]  R. Ross,et al.  TGF-beta induces bimodal proliferation of connective tissue cells via complex control of an autocrine PDGF loop. , 1990, Cell.

[151]  C. Alpers,et al.  Inhibition of mesangial cell proliferation and matrix expansion in glomerulonephritis in the rat by antibody to platelet-derived growth factor , 1992, The Journal of experimental medicine.

[152]  W. Travis,et al.  Cellular and molecular basis of the asbestos-related diseases. , 1991, The American review of respiratory disease.

[153]  C. Wernstedt,et al.  A unique autophosphorylation site in the platelet-derived growth factor alpha receptor from a heterodimeric receptor complex. , 1994, European journal of biochemistry.

[154]  R. Fukuda,et al.  Growth factor mRNA expression in normal colorectal mucosa and in uninvolved mucosa from ulcerative colitis patients , 1996, Journal of Gastroenterology.

[155]  M. Vieth,et al.  Down-regulation of Akt/PKB in senescent cardiac fibroblasts impairs PDGF-induced cell proliferation. , 2001, Cardiovascular research.

[156]  F. Marra,et al.  Extracellular signal‐regulated kinase activation differentially regulates platelet‐derived growth factor's actions in hepatic stellate cells, and is induced by In Vivo liver injury in the rat , 1999, Hepatology.

[157]  V. Paradis,et al.  Expression of connective tissue growth factor in experimental rat and human liver fibrosis , 1999, Hepatology.

[158]  L. Zhang,et al.  Prostaglandin-E2 counteracts interleukin-1beta-stimulated upregulation of platelet-derived growth factor alpha-receptor on rat pulmonary myofibroblasts. , 1999, American journal of respiratory cell and molecular biology.

[159]  H. Fujisawa,et al.  Enhanced interleukin 6 production by cultured fibroblasts from patients with systemic sclerosis in response to platelet derived growth factor. , 1998, The Journal of rheumatology.

[160]  M. Bryckaert,et al.  Increased intraplatelet levels of platelet‐derived growth factor and transforming growth factor‐β in patients with myelofibrosis with myeloid metaplasia , 1991, British journal of haematology.

[161]  R. Ross,et al.  The extracellular glycoprotein SPARC interacts with platelet-derived growth factor (PDGF)-AB and -BB and inhibits the binding of PDGF to its receptors. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[162]  A. Brody,et al.  Chrysotile asbestos upregulates gene expression and production of alpha-receptors for platelet-derived growth factor (PDGF-AA) on rat lung fibroblasts. , 1993, The Journal of clinical investigation.

[163]  J. Lasky,et al.  Modulation of PDGF-C and PDGF-D expression during bleomycin-induced lung fibrosis. , 2004, American journal of physiology. Lung cellular and molecular physiology.

[164]  R. Ross,et al.  Compartmentalization of PDGF on extracellular binding sites dependent on exon-6-encoded sequences , 1992, The Journal of cell biology.

[165]  S. Milani,et al.  Transforming growth factor‐β1 regulates platelet‐derived growth factor receptor β subunit in human liver fat‐storing cells , 1995 .

[166]  C. Cohen,et al.  PDGF-C expression in the developing and normal adult human kidney and in glomerular diseases. , 2003, Journal of the American Society of Nephrology : JASN.

[167]  J. Bonner,et al.  Regulation of PDGFR-α in rat pulmonary myofibroblasts by staurosporine , 2001 .

[168]  D. Anthony,et al.  Transient expression of IL-1beta induces acute lung injury and chronic repair leading to pulmonary fibrosis. , 2001, The Journal of clinical investigation.

[169]  C. Alpers,et al.  Expression of PDGF alpha-receptor in renal arteriosclerosis and rejecting renal transplants. , 1998, Journal of the American Society of Nephrology : JASN.

[170]  Y. Satow,et al.  Platelet derived growth factor expression, myelofibrosis and chronic myelogenous leukemia. , 1995, Leukemia & lymphoma.

[171]  B Swolin,et al.  Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities. , 1994, Genes & development.

[172]  J. Rothberg,et al.  PDGF-D, a new protease-activated growth factor , 2001, Nature Cell Biology.

[173]  A. van Koppen,et al.  PDGF-AB requires PDGF receptor alpha-subunits for high-affinity, but not for low-affinity, binding and signal transduction. , 1993, The Journal of biological chemistry.

[174]  G. Rogler,et al.  Regulation of Migration of Human Colonic Myofibroblasts , 2002, Growth factors.

[175]  M. Goppelt‐Struebe,et al.  Regulation of platelet-derived growth factor isoform-mediated expression of prostaglandin G/H synthase in mesangial cells. , 1996, Kidney international.

[176]  E. Leroy,et al.  Different effects of basic fibroblast growth factor and transforming growth factor-beta on the two platelet-derived growth factor receptors' expression in scleroderma and healthy human dermal fibroblasts. , 1995, The Journal of investigative dermatology.

[177]  J. Bonner,et al.  Basic fibroblast growth factor induces expression of the PDGF receptor-alpha on human bronchial smooth muscle cells. , 1996, The American journal of physiology.

[178]  B. Bhandari,et al.  Platelet-derived growth factor (PDGF) BB homodimer regulates PDGF A- and PDGF B-chain gene transcription in human mesangial cells. , 1994, The Biochemical journal.

[179]  I. Sarosi,et al.  Platelet-derived growth factor causes pulmonary cell proliferation and collagen deposition in vivo. , 1996, The American journal of pathology.

[180]  H. Nishimatsu,et al.  Krüppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling , 2002, Nature Medicine.

[181]  M. Ito,et al.  Interleukin-1 enhances the response of osteoblasts to platelet-derived growth factor through the alpha receptor-specific up-regulation. , 1991, The Journal of biological chemistry.

[182]  H Li,et al.  PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor. , 2000, Nature cell biology.

[183]  D. Graves,et al.  IL-1 and transforming growth factor-beta inhibit platelet-derived growth factor-AA binding to osteoblastic cells by reducing platelet-derived growth factor-alpha receptor expression. , 1993, Journal of immunology.

[184]  A. Gentilini,et al.  Antifibrogenic effects of canrenone, an antialdosteronic drug, on human hepatic stellate cells. , 2003, Gastroenterology.

[185]  J. Reilly.  Pathogenesis and management of idiopathic myelofibrosis. , 1998, Bailliere's clinical haematology.

[186]  J. Bonner,et al.  Regulation of interleukin-1beta -induced platelet-derived growth factor receptor-alpha expression in rat pulmonary myofibroblasts by p38 mitogen-activated protein kinase. , 2000, The Journal of biological chemistry.

[187]  K. Shirato,et al.  Platelet‐derived growth factor, basic fibroblast growth factor, and interferon γ increase type IV collagen production in human fetal mesangial cells via a transforming growth factor‐β‐dependent mechanism , 2000 .

[188]  J. Reveille,et al.  Association of novel polymorphisms with the expression of SPARC in normal fibroblasts and with susceptibility to scleroderma. , 2002, Arthritis and rheumatism.

[189]  Gary R. Grotendorst,et al.  Stimulation of fibroblast cell growth, matrix production, and granulation tissue formation by connective tissue growth factor. , 1996, The Journal of investigative dermatology.

[190]  B. White,et al.  Cytokine regulation of pulmonary fibrosis in scleroderma. , 2003, Cytokine & growth factor reviews.