The Novel Regulatory Mechanism of Fas System-Mediated Apoptosis in Mesangial Cells: Implication to Mesangial Proliferative Glomerulonephritis

Fas Ag is a cell surface molecule that transduces the signal for apoptosis. Since mesangial cells (MC) play important roles in regulating glomerulonephritis, we investigated regulatory mechanisms of Fas system in MC. Fas Ag was expressed on MC from normal mice. This Fas Ag expression was down-regulated by inducing proliferation with platelet-derived growth factor or 18% fetal bovine serum, but was reversed when cycloheximide was added to the culture. Anti-Fas Ab alone did not induce apoptosis in MC, but MC became susceptible to apoptosis induced by anti-Fas Ab if actinomycin D or cycloheximide was added. Noteworthy findings are that mRNA of Fas ligand was expressed in MC. Taken together, MC appears to control the proliferation by regulating Fas system-mediated apoptosis, at least in part, through an autoregulatory mechanism with Fas Ag and Fas ligand expressed on their own MC.