TRANSFORMING GROWTH FACTOR-β1 AND SMAD4 SIGNALING PATHWAY DOWN-REGULATES RENAL EXTRACELLULAR MATRIX DEGRADATION IN DIABETIC RATS

查看全文 作　　者：Qin [1]Yang;Ru-jia [1]Xie;Ting [1]Yang;Li [1]Fang;Bing [1]Han;Guo-zhong [1]Zhang;Ming-liang [2]Cheng

机构地区：[1]Department of Pathophysiology, Guiyang Medical College, Guiyang 550004;[2]Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, Guiyang 550004

出　　处：《Chinese Medical Sciences Journal》索引2007年第22卷第4期,共7页

摘　　要：Objective To investigate the role of transforming growth factor-β1(TGF-β1)/Smad4 pathway in development of renal fibrosis in streptozotocin(STZ)-induced diabetic nephropathy(DN) rats and explore its possible mechanism.Methods Male Wistar rats weighing 180-220 g were divided into 5 groups:group A(normal control),group B [diabetes mellitus(DM) 2 weeks],group C(DM 4 weeks),group D(DM 8 weeks),and group E(DM 16 weeks).Except for the normal control group,other groups were induced DM by single injection of STZ(55 mg/kg) respectively.Blood glucose level,serum creatinine,and 24-hour urine protein were examined.Expressions of TGF-β1 and Smad4 protein and mRNA in kidney were detected using immunohistochemical technique,Western blot,and real-time PCR.mRNA expressions of stromelysin-1(MMP-3),tissue inhibitor of metalloproteinase-1(TIMP-1),and collagen Ⅲ in kidney were also detected by real-time PCR..Results The levels of blood glucose,serum creatinine,and 24-hour urine protein in rats of group B,C,D,and E were higher than those of the control group.With the progression of renal fibrosis,the expressions of TGF-β1 and Smad4 protein and mRNA in kidney of diabetic rats elevated.In addition,the renal MMP-3 mRNA expression diminished in diabetic rats,while TIMP-1 and collagen Ⅲ mRNA increased.Conclusions In STZ-induced diabetic rats,the TGF-β1/Smad4 appears to play an important role in renal fibrosis of DN.The increased expression of TGF-β1 and Smad4 might result in the transcriptional regulation of downstream target genes of TGF-β1/Smad4 pathway,which contributes to the progression of renal fibrosis in diabetic rats. 关键词：糖尿病转化生长因子Β1 肾纤维化动物实验

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TRANSFORMING GROWTH FACTOR-β1 AND SMAD4 SIGNALING PATHWAY DOWN-REGULATES RENAL EXTRACELLULAR MATRIX DEGRADATION IN DIABETIC RATS

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