title: Leukemia inhibitory factor attenuates renal fibrosis through Stat3-miR-29c.
abstract: Leukemia inhibitory factory (LIF), as a member of the IL-6 family, has been reported to ameliorate myocardial fibrosis and myocardial cell death. The purpose of the present study was to investigate the effect of LIF on renal fibrosis and its underlying mechanism. Our results showed, first, that LIF inhibited collagen type 1 and collagen type 3 expression induced by ANG II in NRK-49F (rat kidney fibroblast) cells and in mice with unilateral ureteral obstruction. Second, LIF induced Stat3 Tyr(705) phosphorylation and inhibited Stat3 Tyr(705) and Ser(727) phosphorylation induced by ANG II in NRK-49F cells. Third, LIF exerted an antirenal fibrosis effect mainly through activation of Stat3 Tyr(705) phosphorylation in NRK-49F cells. These effects of LIF were not observed in Stat3(-/-) cells. Finally, LIF-Stat3 upregulated microRNA-29c expression, and the latter downregulated collagen type 1 and collagen type 3 expression in NRK-49F cells and in mice with unilateral ureteral obstruction. In conclusion, LIF played a role in antirenal fibrosis by competitively activating Stat3 Tyr(705) phosphorylation, which upregulated microRNA-29c to suppress collagen expression.
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China; and.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Shanghai, China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China; and.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China; and.
authors.forename: Lanjun
authors.initials: L
authors.lastname: Fu
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Shanghai, China yuchen@tongji.edu.cn.
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Chin
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China; and.
authors.forename: Chen
authors.initials: C
authors.lastname: Yu
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis; D024061:Collagen Type III / Q000096:biosynthesis; D019295:Computational Biology; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D005355:Fibrosis; D055785:Gene Knockdown Techniques; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy* / Q000473:pathology; D053605:Leukemia Inhibitory Factor / Q000627:therapeutic use*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009395:Nephritis, Interstitial / Q000473:pathology; D051381:Rats; D050796:STAT3 Transcription Factor / Q000235:genetics*; D014162:Transfection; D014517:Ureteral Obstruction / Q000473:pathology
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D016326:Extracellular Matrix Proteins; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C526366:MIRN29 microRNA, rat; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; D000804:Angiotensin II
keywords: extracellular matrix; leukemia inhibitor factor; microRNA-29c; renal fibrosis; signal transducer and activator of transcription 3