Transcriptional regulation of the A and B chain genes of platelet-derived growth factor in microvascular endothelial cells

Abstract

Platelet-derived growth factor is expressed as dimers of two homologous polypeptide chains, termed A and B, encoded by different genes. A and B chain mRNA levels in microvascular endothelial cells are increased by phorbol ester, thrombin, and transforming growth factor-beta (TGF-beta) and are reduced by agents that elevate cyclic AMP. In this report, we investigated the effects of these regulatory agents on A and B chain transcription rates. By nuclear run-on analysis, TGF-beta stimulated transcription of both A and B chain genes. Thrombin and phorbol ester stimulated B chain transcription and had little or no detectable effect on A chain transcription. Pretreatment of cultures with 50 microM forskolin, a potent activator of adenylyl cyclase, completely blocked B chain transcription by thrombin and TGF-beta, but did not inhibit A chain transcription induced by TGF-beta. These results show that expression of platelet-derived growth factor mRNA involves both positive and negative transcriptional regulation and that there are differences in the transcriptional control of the A and B chain genes.