Platelet-derived growth factor, basic fibroblast growth factor, and interferon gamma increase type IV collagen production in human fetal mesangial cells via a transforming growth factor-beta-dependent mechanism.

BACKGROUND: Glomerulosclerosis is characterized by glomerular accumulation of extracellular matrix following mesangial cell proliferation. The precise pathomechanism of glomerulosclerosis is still undetermined. Platelet-derived growth factor (PDGF) and basic fibroblast growth factor (b-FGF) are known to be mitogenic for mesangial cells, and interferon gamma (IFN-gamma) is known to have an inhibitory effect on mesangial cell proliferation. We attempted to clarify the role of these cytokines on mesangial matrix production using cultured human fetal mesangial cells (HMC). METHODS: HMC were incubated with these cytokines for 24-72 h and the levels of type IV collagen and TGF-beta in the cell supernatants were measured by enzyme immunoassay. RESULTS: PDGF, b-FGF, and IFN-gamma stimulated type IV collagen production by HMC in a dose- and time-dependent manner. The anti-TGF-beta neutralizing antibody clearly inhibited their stimulatory effect on type IV collagen production. PDGF and b-FGF also stimulated TGF-beta production by HMC in a dose-dependent manner, although IFN-gamma did not. CONCLUSION: PDGF, b-FGF, and IFN-gamma stimulate type IV collagen production in cultured HMC via a TGF-beta-dependent mechanism.