Platelet-derived growth factor (PDGF) family of mesenchymal mitogenic factors consists of four homodimers (PDGF-AA, PDGF-BB, PDGF-CC and PDGF-DD) and one heterodimer (PDGF-AB). These proteins are expressed by a number of different cells and tissues including endothelial cells, epithelial cells, hematopoietic cells, connective tissue, nervous tissue, brain, muscle, kidney and liver. PDGF expression is highly regulated with PDGF levels increasing following injury and/or disease. An analysis of PDGF purified from human platelets suggest that approximately 70% of sera-derived PDGF is PDGF-AB (1).
PDGF isoforms exert their cellular effect by binding to the structurally similar receptor tyrosine kinases PDGF receptor-alpha and PDGF receptor-beta. PDGF-AB binding induces receptor dimerization resulting in alpha alpha receptor homodimers and alpha beta receptor heterodimers. Binding of PDGF receptors has been reported to result in stimulation of mitogenicity and chemotaxis of fibroblasts, stimulation of granule release by neutrophils and monocytes, facilitation of steroid synthesis by Leydig cells, stimulation of neutrophil phagocytosis, stimulation of collagen, fibronectin, proteoglycan, and hyaluronic acid synthesis, modulation of thrombospondin expression and secretion, stimulation of collagenase activity and secretion, induction of contraction of rat aorta strips in vitro, and transient induction of T cell IL-2 secretion accompanied by a down-regulation of IL-4 and IFN-gamma production (2).
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