Induction of platelet-derived growth factor alpha- and beta-receptor mRNA and protein by platelet-derived growth...

We describe that stimulation of human fibroblasts with platelet-derived growth factor BB (PDGF-BB) induces a transient up-regulation of the PDGF alpha- and beta-receptor transcript and protein levels. The effect of PDGF-BB on the receptor transcript levels was more pronounced than those seen when other cytokines were used. Regulation of transcript levels by PDGF-BB was mediated through post-transcriptional mechanisms. No induction could be observed in a nuclear run-on analysis, but cycloheximide treatment attenuated the accumulation of both alpha- and beta-receptor transcripts induced by PDGF-BB. An increase in receptor protein levels was observed using two different experimental approaches. Increased amounts of receptor precursor forms could be immunoprecipitated from metabolically labeled cells, stimulated with PDGF-BB. In a second approach, cells were exposed to different concentrations of PDGF-BB, and, in a subsequent step, ligand binding analysis was performed. In this experiment, an initial down-regulation of receptors was followed by increased levels of the cell surface forms of the receptors. In conclusion, PDGF-BB, but not PDGF-AA, induces increased synthesis of both PDGF alpha- and beta-receptor protein; this constitutes a positive feed-back mechanism, which, for example, could serve to potentiate autocrine stimulation of growth.