Expression of PDGF α- and β-receptors in Rat Arterial Smooth Muscle Cells is Phenotype and Growth State Dependent

Abstract

Adult rat arterial smooth muscle cells were shown to express mRNA for the platelet-derived growth factor (PDGF) alpha- and beta-receptors and to bind radioiodinated PDGF-AA and PDGF-BB in a phenotype-dependent and growth state-dependent manner. PDGF alpha-receptor mRNA was not detected in the intact aortic media, but appeared as the cells converted from a contractile to a synthetic phenotype during serum-free primary culture. PDGF beta-receptor mRNA was expressed already in vivo, and increased further as the cells were isolated and cultured in vitro. Exposure of the cells to human platelet PDGF resulted in increased PDGF alpha-receptor mRNA levels, decreased PDGF beta-receptor mRNA levels, and decreased binding of both PDGF-AA and PDGF-BB. Following removal of the exogenous mitogen, the content of PDGF alpha- and beta-receptor mRNA increased, as did the binding of PDGF-AA and PDGF-BB. Subsequently, the content of PDGF A-chain mRNA started to rise, and the cells retained a high rate of DNA synthesis in a serum-free medium. As a result of this autocrine stimulation, the PDGF receptors were down-regulated. Although smooth muscle cells in serum-free primary cultures bound the different PDGF isoforms to a varying extent (AA less than AB less than BB), the replicative response was of a similar magnitude. Subcultured cells bound the different PDGF isoforms in similar proportions as the primary cells. Contrary to the situation in primary cells, there was a direct correlation between the binding level and the DNA synthetic response. Moreover, the subcultured cells did not replicate in a serum-free medium. These observations support the idea that the phenotypic modulation of arterial smooth muscle cells in primary culture prepares the cells to activate autocrine growth mechanisms. When stimulated with an exogenous mitogen, they enter the cell cycle and are thereafter able to stimulate their own growth in an autocrine manner by production of PDGF-AA or a closely related molecule.