EGFR-JNK Signaling Pathway In Rat Glomerular Mesangial Cells Proliferation And Effect Of Heparin On It

Objective Heparin is a well proliferation inhibitor of glomerular mesangial cells (GMCs) both in animal models and in vitro, but the exact mechanism has still not been explained. The aims of this study were to investigate whether the EGFR-JNK Signaling Pathway play an important role in rats GMCs Proliferation and the effect of heparin In It.Methods Four groups were established: GMCs group, LPS group (GMCs+ LPS), heparin groups (GMCs+ LPS+ heparin), AG1478 group (GMCs+ LPS+ AG1478). GMCs proliferation were detected by MTT at 24h after be culture. The expressions of EGFR and P-JNK were assayed by western blot and immunohistochemisty.Results (1) In the heparin group with the concentration of 250ug/ml and the AG1478 group of the concentration of 20umol/L, the proliferation of GMCs were lower than in the LPS group and 100ug/ml, 500ug/ml heparin groups (p<0.01). (2) On normal culture condition, GMCs can express a certain amount of EGFR and P-JNK, the expression is up-regulated in LPS group (p<0.01), the expression of EGFR and P-JNK in heparin groups were lower than in LPS group (p<0.05), but there was no statistical difference when compared with the GMCs group. (3) The expression of P-JNK in AG1478 group was lower than that in LPS group (p<0.05), and did not differ from that in heparin groups and GMCs groups.Conclusion The moderate concentration of heparin and AG1478 can obviously inhibit the proliferation of GMCs which induced by LPS, the heparin can inhibit the proliferation of GMCs by down-regulate the EGFR-P-JNK signaling pathway.