Role of Growth Factors in the Pathogenesis of Tissue Fibrosis in Systemic Sclerosis
Sergio A. Jimenez,
Susan V. Castro,
The most severe clinical and pathologic manifestations of systemic sclerosis (SSc) are the result of a fibrotic process characterized by the excessive and often progressive deposition of collagen and other connective tissue macromolecules in skin and numerous internal organs. The mechanisms involved in the initiation and progression of the remarkable fibrotic process in SSc remain largely unknown. Extensive recent studies have indicated that a variety of polypeptide growth factors play a crucial role in this process. The most commonly implicated growth factors include transforming growth factor beta (TGF-β), connective tissue growth factor (CTGF), platelet derived growth factor (PDGF), and vascular endothelial growth factor (VEGF). Here, the experimental evidence supporting the participation of various growth factors in the pathogenesis of the fibrotic process in SSc and the molecular mechanisms involved will be reviewed.
Keywords: Systemic sclerosis, fibrosis, growth factor, c-Abl, protein kinase c delta, imatinib mesylate, fibrotic process, connective tissue growth factor (CTGF), platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), myofibroblasts, extracellular matrix, pathologic organ fibrosis, contractile phenotype, phenotypic transdifferentiation, EndoMT, polypeptide growth, growth factors, Transforming Growth Factor Beta (TGF-β), malignant cell transformation, vascular morpho-genesis, inflammatory response, wound healing,, latency-associated peptide (LAP), (LTBP), TGF-β Signaling, activin receptor like kinases, (RSmads), SARA, Cytoplasmic Abelson Kinase (c-Abl), chronic myelogenous leukemia, PI3K/Akt Pathways, Caveolin-1 Regulation, fibrotic diseases, collagens type, TGF-β mediated pathways., TGF-β pleotropic effects, αvβ5 expression, anti-αvβ5 antibody, β5 antisense oligonucleotide, therapeutic target, SSc Pathogenesis, profiling technologies, high-resolution expression, Global gene expression, healthy control biopsies, pathological tissue fibrotic responses, GTPase activa-ting protein (IQGAP), Platelet-Derived Growth Factor (PDGF), BAL fluid, selective tyrosine kinase inhibitors, anti-PDGF receptor-specific, reactive oxygen radicals (ROS), serum autoantibodies, colony-stimulating factor receptor 1, anti-PDGFRa, Fibroblast Growth Factors (FGF), Insulin-Like Growth Factor (IGF), systemic lupus erythematosus, IGF-1, IGFBP-3, SSc-associated pulmonary fibrosis, intracellular signaling cascades
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