Platelet-derived growth factor: a key regulator of connective tissue cells in embryogenesis and pathogenesis

Studies of PDGF-A, PDGF-B and PDGF receptor-beta knock-out mice have revealed critical functions for the PDGF-PDGF receptor signaling systems in the ontogeny of connective tissue cells: the mesangial cells of kidney glomeruli and the alveolar smooth muscle cells (SMC) of the lung. The phenotypes of the PDGF mutant mice have also shed light on the identity and functions of these cell types, as well as revealed analogies suggesting that common morphogenetic principles have evolved for use in different organs, involving related growth factors and cell types. Although the lethality of PDGF knock-out mice has not allowed an investigation of the role of PDGF in SMC of the vessel wall, regulation of PDGF and its receptors in adult vessels following injury is consistent with a role for PDGF in the fibroproliferative response in the intima that occurs as part of the pathogenesis of atherosclerosis. PDGF modulation of connective tissue synthesis may thus be critical to connective tissue phenotype and proliferation in both embryogenesis and pathogenesis.