Downregulation of p38 MAPK Involved in Inhibition of LDL-induced Proliferation of Mesangial Cells and Matrix by Curcumin

Curcumin, as a main pharmacological component in the traditional Chinese medicine-- tttrmeric, has shown anti-inflammatory, anti-oxidation, anti-tumor and anti-fibrotic effects. This study aimed to investigate the possible underlying signaling pathway which was involved in the inhibition of LDL-induced proliferation of mesangial cells and matrix by curcumin. Rat mesangial cells in vitro were incubated with low-density lipoprotein （LDL） and different concentrations of curcumin （0, 6.25, 12.5, 25.0 9mol/L） or p38 MAPK inhibitor, SB203580 （10 μmol/L）. Under LDL incubation, mesangial cells proliferated, the expression of MMP-2 mRNA and protein was decreased, the expression of COX-2 mRNA and protein was increased, reactive oxygen species （ROS） generation was increased and p38 MAPK was activated significantly （P〈0.05）. When LDL-induced cells were treated with curcumin in the concentration of 12.5 or 25.0 μmol/L, LDL-induced proliferation ofmesangial cells was suppressed, the expression of MMP-2 mRNA and protein increased, the expression of COX-2 mRNA and protein downregulated, the production of ROS inhibited and p38 MAPK inactivated （P〈0.05）. In conclusion, curcumin can inhibit the LDL-induced proliferation of mesangial cells and up-regulate the expression of MMP-2, which may be related with the inhibitory effect of curcumin on COX-2 expression, ROS pro- duction and p38 MAPK.