In this study we have investigated both the expression of c-met in cultured human mesangial cells and the proliferative effect of HGF on these cells. RNAse protection analysis using a c-met riboprobe showed c-met to be expressed and further that this expression was unaffected by the glucose concentration or osmolality of the media. Immunofluorescence studies performed using anti-HGF or anti-c-met antibodies clearly showed that both proteins are localised to human mesangial cells. Proliferation of human mesangial cells after 24-h treatment with HGF was also examined. HGF 10 ng/ml and 100 ng/ml stimulated 3-H-Thymidine incorporation 1.35-fold (P = 0.001) and 1.6-fold (P<0.00001) respectively in cells made quiescent for 24 h. A similar dose-dependent stimulation of proliferation was observed in cells made quiescent for 48 h. Finally, using RNAse protection analysis we have shown that HGF (10 ng/ml, 100 ng/ml) induces the expression of c-met in these cells in a dose-dependent manner. Together these results indicate for the first time a potential autocrine role for HGF in the human mesangium.