The Study Of Extracellular Matrix Metalloproteinase Inducer In Diabetic Nephropathy

Objectives 1.To observe the effects of high glucose concentration on the expression of EMMPRIN in kidneys and to explore the mechanisms of diabetic nephropathy by examining the expression of EMMPRIN. 2.To observe the effects of high ambient glucose concentration on the expression of EMMPRIN,MMP-2 in human glomerular mesangial cells in vitro and to explore further the mechanism of glomerular extracellular matrix accumulation in diabetic nephropathy.Methods 1.Rat diabetic model was induced by streptozotocin (55mg/kg),and the histology of kidneys was observed and the expression of EMMPRIN,MMP-2,CTGF,PDGF was examined by immunohistochemistry. 2.The mesangial cells were cultured in the high glucose media for 0h,12h,24h and 48h, respectively.The expression of EMMPRIN and MMP-2 mRNA was measured by RT-PCR and the protein expression of EMMPRIN and MMP-2 was observed by immunocytochemistry.Results 1.EMMPRIN and MMP-2 were mainly expressed in the mesangial cells,endothelial cells, podocytes, parietal epithelial cells of Bowman's capsule,and tubular cells. The expression of EMMPRIN and MMP-2 was significantly weaken in the glomeruli of diabetic rats than that of the control animals(P<0.05). The expression of PDGF and CTGF was significantly enhenced in the glomeruli of diabetic rats than that of the control animal. 2.Compared with control groups, the expression of mRNA and protein expression of EMMPRIN and MMP-2 in the mesangial cells cultured in high glucose decreased(P<0.05).Conclusions 1.The increasing synthesis of many matrix components was not the only reason for the accumulation of glomerular extracellar matrix (ECM) in diabetic nephropathy.The decreasing degradation of matrix also plays a very important role in the accumulation of ECM. 2.These results demonstrated for the first time that EMMPRIN is downregulated in diabetic nephropathy.Decreased EMMPRIN may contribute to decreased degradation of the matrix. 3.High glucose down-regulates the mRNA and protein expression of EMMPRIN and MMP-2 in the mesangial cells.The decreased expression of EMMPRIN may alter the expression of MMPs in mesangial cell,thus influence the degradation of ECM in diabetic nephropathy.