Kidney epithelial cells express c-sis protooncogene and secrete PDGF-like protein

Nontransformed monkey kidney cells (BSC-1 line), used as a model for renal epithelium, were assayed for release of platelet-derived growth factor (PDGF)-like proteins. BSC-1 cells continuously released a mitogenic activity for fibroblasts and a chemoattractant activity for smooth muscle cells, each of which was inhibited 80-90% by an antibody to human PDGF. A cDNA probe for the PDGF B-chain gene (c-sis), but not for the A-chain gene, hybridized to mRNA obtained from growing and quiescent cells. c-sis gene expression and PDGF-like protein secretion were studied in the presence of known growth-regulatory molecules. A secreted BSC-1 cell protein identical to transforming growth factor beta 2 inhibited DNA synthesis in growing cultures and induced marked accumulation of c-sis mRNA without a corresponding increase in the release of PDGF-like activity. Adenosine diphosphate stimulated DNA synthesis in quiescent cultures and enhanced both c-sis expression and release of PDGF-like activity. However, growing and quiescent cells did not express the PDGF receptor gene or exhibit a mitogenic response to authentic PDGF. Thus the PDGF-like protein released by these kidney epithelial cells could contribute to growth control by a paracrine mechanism.