VEGF regldates the expression of MMPs and TIMPs in mouse mesangial cells

Objective To study the regulation of MMPs and TIMPs expression by VEGF in mouse mesangial cells (MMCs) . Methods Cultured MMCs were incubated with or without recombinant human VEGF for 12 hours. Protein levels of MMP2,MMP9,TIMP1 and TIMP2 in media were measured by Western blot analysis. MMP2 and MMP9 activities were measured by gelatin zymography. TIMP1 and TIMP2 mRNA expression in MMCs was analyzed by RT-PCR. Results VEGF(10 ng/ml) upregulated MMP2 and MMP9 protein secretion by MMCs (increased by 43% and 34% respectively, P 0. 05) when compared with control. MMP2 and MMP9 activities also increased by 17% and 26% ( P 0. 05) respectively. Simultaneously, VEGF downregulated TIMP1 and TTMP2 protein secretion and mRNA expression by MMCs in a dose-dependent manner. VEGF(25 ng/ml) decreased TIMP1 and TIMP2 protein secretion by 43% and 67% (P 0. 05) and suppressed TIMP1 and TIMP2 mRNA expression by 41% and 59% , respectively ( P 0. 01) by MMCs. Conclusion VEGF increases MMPs excretion and activity but suppresses TIMPs protein and mRNA expression by MMCs, which may promote cell proliferation and ECM accumulation in proliferative glomerulonephritis.