Abstract
Platelet-derived growth factor (PDGF) isoforms are polypeptide mediators that play a major role in stimulating the replication, survival, and migration of mesenchymal cells during the pathogenesis of fibrotic diseases. PDGF is secreted by a variety of cell types including epithelial cells, macrophages, and fibroblasts as a response to injury, and many proinflammatory cytokines mediate their mitogenic effects via the autocrine release of PDGF. PDGF-A and PDGF-B chain dimeric isoforms (PDGF-AA, PDGF-AB, and PDGF-BB) play important roles in the pathogenesis of fibrosis. These isoforms promote myofibroblast proliferation and chemotaxis, but also serve other functions including stimulation of collagen production and promotion of cell adhesion. Less is known regarding the significance of the more recently discovered PDGF-C and PDGF-D chain isoforms. The biological activity of PDGF is determined by the relative expression of PDGF α-receptors and β-receptors on the cell surface. These receptors are induced during lung fibrogenesis, thereby amplifying biological responses to PDGF isoforms. PDGF action is further modulated in the extracellular milleau by binding proteins, matrix molecules, and proteases.
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