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Losartan Alleviates Renal Fibrosis and Inhibits Endothelial-to-Mesenchymal Transition (EMT) Under High-Fat Diet-Induced Hyperglycemia

文献类型： 外文期刊

作者： Yao, Yufeng 2 ; Li, Yong 1 ; Zeng, Xiaofei 3 ; Ye, Zheng 4 ; Li, Xia 5 ; Zhang, Lu 6 ;

作者机构： 1.Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Minist Educ, Key Lab Mol Biophys, Wuhan, Hubei, Peoples R China

2.Huazhong Univ Sci & Technol, Ctr Human Genome Res, Wuhan, Hubei, Peoples R China

3.Wuhan Univ, Coll Life Sci, Wuhan, Hubei, Peoples R China

4.Southeast Univ, Coll Biol Sci & Med Engn, Nanjing, Jiangsu, Peoples R China

5.Guangdong Acad Agr Sci, Inst Agr Resources & Environm, Guangzhou, Guangdong, Peoples R China

6.Huazhong Univ Sci & Technol, Wenhua Coll, Wuhan, Hubei, Peoples R China

关键词： EMT; diabetic nephropathy; TGF-beta 1/Smad signaling; losartan; oxidative stress

期刊名称：FRONTIERS IN PHARMACOLOGY （ 影响因子：5.81； 五年影响因子：6.005 ）

ISSN： 1663-9812

年卷期： 2018 年 9 卷

页码：

收录情况： SCI

摘要： The endothelial-to-mesenchymal transition (EMT) of glomerular vascular endothelial cells is considered to be pivotal in diabetic nephropathy (DN). The risk of DN can be decreased by losartan, but the potential molecular mechanism(s) are not fully understood. Extensive data show that the EMT occurs in proximal tubular endothelial cells resulting in an endothelial phenotype switch (fibrotic matrix accumulation), consequently enhancing the development of renal interstitial fibrosis. Here, we found that losartan significantly ameliorated DN-induced renal fibrosis progression via inhibition of the EMT in mice. In vivo experiments suggested that losartan significantly alleviated microalbuminuria and pathologic changes under high-fat diet-induced hyperglycemia. Immunohistochemistry indicated that losartan suppressed the EMT in glomeruli. In addition, losartan decreased oxidative stress damage and inhibited the transforming growth factor (TGF)-beta 1 /Smad pathway. Furthermore, consistent changes were detected in vitro where losartan markedly inhibited the EMT and TGF-beta 1/Smad pathway induced by high glucose in glomerular endothelial cells. Together, these results suggested that losartan could alleviate the EMT in glomeruli via inhibition of oxidative stress damage and the TGF-beta 1/Smad signaling pathway under hyperglycemia.

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