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.
Bonner
James C
JC
National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. jbonner@ciit.org
D000818:Animals; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis / Q000473:pathology*; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007375:Interleukin-1 / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008954:Models, Biological; D009132:Muscles / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000502:physiology*; D020033:Protein Isoforms; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000473:pathology; D015398:Signal Transduction; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D020033:Protein Isoforms; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta