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作者

Duan, L.-J. Ding, M. Hou, L.-J. Cui, Y.-T. Li, C.-J. Yu, D.-M.

作者单位

a Department of Endocrinology, Tianjin First Central Hospital, Tianjin, 300192, China Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, 300070, China Department of Thoracic Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, China Department of Endocrinology, The Affiliated Hospital of Taishan Medical University, Tai'an, 271000, China

刊名

Biochemical and Biophysical Research Communications

年份

2017

卷号

Vol.484 No.3

页码

598-604

ISSN

0006-291X

关键词

diabetic nephropathy Extracellular matrix Long noncoding RNA Mesangial cell miRNA-377 PPARγ TUG1

摘要

Long noncoding RNA taurine-upregulated gene 1 has been reported to play a key role in the progression of diabetic nephropathy . However, the role of lncRNA TUG1 in the regulation of diabetic nephropathy remains largely unknown. The aim of the present study is to identify the regulation of lncRNA TUG1 on extracellular matrix accumulation via mediating microRNA-377 targeting of PPARγ, and investigate the underlying mechanisms in progression of DN. Microarray was performed to screen differentially...更多

Long noncoding RNA taurine-upregulated gene 1 has been reported to play a key role in the progression of diabetic nephropathy . However, the role of lncRNA TUG1 in the regulation of diabetic nephropathy remains largely unknown. The aim of the present study is to identify the regulation of lncRNA TUG1 on extracellular matrix accumulation via mediating microRNA-377 targeting of PPARγ, and investigate the underlying mechanisms in progression of DN. Microarray was performed to screen differentially expressed miRNAs in db/db DN mice. Afterwards, computational prediction programs was applied to predict the target gene of miRNAs. The complementary binding of miRNA and lncRNA was assessed by luciferase assays. Protein and mRNA expression were detected by western blot and real time quantitate PCR. MiRNA-377 was screened by miRNA microarray and differentially up-regulated in db/db DN mice. PPARγ was predicted to be the target of miR-377 and the prediction was verified by luciferase assays. Expression of miR-377 was up-regulated in mesangial cell treated with high glucose , and overexpression of miR-377 inhibited PPARγ expression and promoted PAI-1 and TGF-β1 expression. The expression of TUG1 antagonized the effect of miR-377 on the downregulation of its target PPARγ and inhibited extracellular matrix accumulation, including PAI-1, TGF-β1, fibronectin and collagen IV , induced by high glucose. LncRNA TUG1 acts as an endogenous sponge of miR-377 and downregulates miR-377 expression levels, and thereby relieving the inhibition of its target gene PPARγ and alleviates extracellular matrix accumulation of mesangial cells, which provides a novel insight of diabetic nephropathy pathogenesis.收起

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