Proliferation of renal mesangial cells induced by very low density lipoprotein is mediated by p42/44 mitogen activated protein kinase

Background The plasma concentration of very low density lipoprotein (VLDL) is negatively correlated to renal function in glomerular diseases. Effects of VLDL on renal function have been partially attributed to the proliferation of mesangial cells. This study examined the potential role of the p42/44 mitogen activated protein kinase (MAPK) in mesangial cell proliferation induced by VLDL.Methods Mesangial cells were treated with VLDL at different concentrations or for different time. The cell cycle of the mesangial cells was analyzed by XTi assay and flow-cytometry; MAPK activity was also assayed. In some experiments,cells were treated with VLDL together with or without 0.1 μmol/L PD 98059.Results Ten to 500 μg/ml VLDL stimulated the proliferation of mesangial cells cultured in vitro in a concentration-dependent manner. The effect was associated with an increase in p42/44 MAPK activity. Increased proliferation of mesangial cells by VLDL was significantly attenuated by PD98059, a specific p42/44 MAPK inhibitor.Conclusion These results indicate that the p42/44 MAPK pathway is an important regulator of mesangial cell proliferation and of renal functions.