title: Long noncoding RNA TUG1 alleviates extracellular matrix accumulation via mediating microRNA-377 targeting of PPARγ in diabetic nephropathy.
abstract: Long noncoding RNA taurine-upregulated gene 1 (lncRNA TUG1) has been reported to play a key role in the progression of diabetic nephropathy (DN). 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 (TargetScan, miRanda, PicTar and miRGen) 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 (25 mM), 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 (FN) and collagen IV (Col 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.
authors.affiliation: Department of Endocrinology, Tianjin First Central Hospital, Tianjin, 300192, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Duan
authors.affiliation: 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.
authors.forename: Min
authors.initials: M
authors.lastname: Ding
authors.affiliation: Department of Endocrinology, The Affiliated Hospital of Taishan Medical University, Tai'an, 271000, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Hou
authors.affiliation: Department of Thoracic Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, China.
authors.forename: Yuan-Tao
authors.initials: YT
authors.lastname: Cui
authors.affiliation: 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. Electronic address: lichunjun_lucky@163.com.
authors.forename: Chun-Jun
authors.initials: CJ
authors.lastname: Li
authors.affiliation: 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. Electronic address: yudemin_line@126.com.
authors.forename: De-Min
authors.initials: DM
authors.lastname: Yu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D050527:Mesangial Cells / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; C534064:Mirn377 microRNA, mouse; D047495:PPAR gamma; D062085:RNA, Long Noncoding; C000619335:TUG1 long noncoding RNA, rat; C000619856:long non-coding RNA TUG1, mouse
keywords: Extracellular matrix; Long noncoding RNA; Mesangial cell; PPARγ; TUG1; diabetic nephropathy; miRNA-377