TGF-beta stimulates primary human skin fibroblast DNA synthesis via an autocrine production of PDGF-related peptides

Abstract

Transforming growth factor-beta (TGF-beta) stimulates DNA synthesis in human foreskin fibroblasts after a prolonged lag period as compared with other growth factors. The mechanism of induction of DNA synthesis appears to be dependent on the synthesis and secretion of PDGF-related proteins as antibodies which are specific for PDGF can block the TGF-beta-induced DNA synthesis. Other growth factors such as PDGF, EGF, or FGF do not induce the synthesis of these PDGF-related proteins. Additionally, TGF-beta treatment of human foreskin fibroblasts induces the expression of the PDGF A-chain gene but not the B-chain gene. This phenomenon appears to function in vivo, as subcutaneous injection of TGF-beta in rat skin induces the expression of the PDGF A-chain gene. These data suggest that TGF-beta may stimulate the growth of fibroblastic cells via an autocrine production of PDGF-related proteins.