Abstract: Objective To investigate the beneficial effect of hepatocyte growth factor(HGF) on diabetic nephropathy(DN),and to observe the effect of HGF on the degradation of extra-cellular matrix(ECM) and production of TGF-β1 in cultured rat glomerular mesangial cells under high glucose condition.Methods MTT colorimetry was used to detect the proliferation of rat mesangial cells cultured under various concentrations of glucose and HGF.Then the cultured mesangial cells were divided into three groups as following:1) normal control group:the concentration of glucose in medium was 5 mmol/L;2) high glucose group:the concentration of glucose in medium was 30 mmol/L;3) HGF treatment group:the concentration of glucose in medium was 30 mmol/L and concentration of HGF is 50 μg/L.These cells were cultured for 48 hours.Then the supernatant content of TIMP-1,MMP-9,TGF-β1,HGF and Ⅳ collagen were measured by ELISA and the level of TIMP-1,MMP-9,TGF-β1,HGFmRNA were measured by RT-PCR.Results 1) HGF suppressed the proliferation induced by high glucose in cultured mesangial cells.2) High glucose concentration could stimulate the secretion of TIMP-1,TGF-β1,Ⅳcollagen and reduce the secretion of MMP-9.Compared to the high glucose group,HGF could suppress the secretion of TIMP-1,TGF-β1,and Ⅳ collagen but had little effect on MMP-9.3) Compared to high glucose group,the expression of TIMP-1mRNA and TGF-β1mRNA were significantly decreased in HGF treated group,while the expression of MMP-9mRNA and HGFmRNA were significantly upregulated.Conclusion The results suggest that HGF can protect the cultured mesangial cells from injury of high glucose concentration.This protective effect of HGF is exerted through the following mechanisms:HGF inhibit the proliferation of the mesangial cells under high glucose condition;increases ECM degradation by modulation of the balance between MMP-9 and TIMP-1;suppresses the secretion of TGF-β1 and upregulates the expression of HGF to rebuild the balance between TGF-β1 and HGF.

Key words: hepatocyte growth factor, mesangial cell, diabetic nephropathy, matrix metalloproteinases, transforming growth factor-β1