HGF Regulates The Expression Of MMP-2, -9 In Rat Mesangial Cells

The hallmark of glomerular sclerosis is the relentless accumulation of extracellular matrix (ECM) , which is believed to result from an imbalance in synthe-sion and degradation. ECM degradation is tightly controlled by a family of zinc-dependent matrix-degrading enzymes known as matrix metalloproteinase (MMPs). Hepatocyte growth factor (HGF) has been shown to reduce netECM accumulation by increasing MMPs expression in renal tubular cells, however whether HGF also modulates the development and progression of glomerular sclerosis by activating matrix degradation pathways in renal mesangial cells is uncertain.ObjectiveTo study the regulation of expression of MMP -2,-9 and ECM secretion by HGF in rat mesangial cells ( RMC) .MethodsCultured RMC were incubated with different concertration recombinant human HGF(0 ~75ng/ml) for 24 hours, cell proliferation was assessed by MTT colorimetric assay, protein levels of MMP-2,-9 and Fibronectin ( FN) in the RMC were measured by western blotting analysis, and MMP-2, -9 activities were measured by gelatin zymography.ResultsAdministration 0 ~25ng/ml HGF into culture medium had no effect on proliferation of RMC, in this range, HGF upregulate MMP-9 activities (increased by 57% ,p <0. 05) when compared with control, and its protein secretion by RMC also increased by 15%. MMP-2 was normally expressed, at a very low level, in the cells, and HGF had no effect on its protein expression. Zymogra-phy showed that no degradtive activity of MMP-2 in serum-free RMIP1640 was observed, while we can detect its activity at a low level by HGF (10 ~ 25ng/ ml). Moreover HGF decreases the protein expression of FN by 42% compared with the control.ConclusionHGF can stimulate MMP -2,-9 activities and MMP-9 protein secretion in various degree, also increased the degradation of FN, which may inhibite accumulation of ECM and delay progressive of glomerulosclerosis.