Platelet-derived growth factor synthesis in mesangial cells: induction by multiple peptide mitogens

Abstract

Platelet-derived growth factor (PDGF) has been implicated in several nonmalignant pathophysiological processes, including proliferative diseases of the kidney. Glomerular mesangial cells secrete a PDGF-like factor and express the PDGF A-chain and c-sis (or B-chain) mRNAs. We report here that both mRNAs are induced by serum and this effect can be mimicked by recombinant PDGF, which also markedly stimulates DNA synthesis. Other growth factors, such as epidermal growth factor (EGF), transforming growth factor type alpha, basic fibroblast growth factor (bFGF), and tumor necrosis factor type alpha (TNF-alpha) also are mitogenic for human mesangial cells and induce expression of the PDGF mRNAs. EGF, TNF-alpha, and bFGF also stimulate these cells to secrete a PDGF-like factor. Furthermore, anti-PDGF antibody partially abrogates the mitogenic effect of EGF, suggesting that mitogen-stimulated PDGF synthesis in mesangial cells is at least partly responsible for cell growth induced by other growth factors. In contrast to these results, transforming growth factor type beta (TGF-beta), while inducing both mRNAs, is not mitogenic, indicating that its effect on message levels can be dissociated from DNA synthesis. These data suggest that several peptide growth factors regulate the growth of mesangial cells and that PDGF may be an effector molecule that plays a role in the mitogenic response to many of these growth stimuli.