Leukemia inhibitory factor attenuates renal fibrosis through Stat3-miR-29c.
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.
['Yu|Ying|Y|', 'Wang|Yumei|Y|', 'Niu|Yangyang|Y|', 'Fu|Lanjun|L|', 'Chin|Y Eugene|YE|', 'Yu|Chen|C|']
D000804:Angiotensin II D000818:Animals D002478:Cells, Cultured D024042:Collagen Type I D024061:Collagen Type III D019295:Computational Biology D016326:Extracellular Matrix Proteins D005355:Fibrosis D055785:Gene Knockdown Techniques D015850:Interleukin-6 D007668:Kidney D007674:Kidney Diseases D053605:Leukemia Inhibitory Factor D051379:Mice D035683:MicroRNAs D009395:Nephritis, Interstitial D051381:Rats D050796:STAT3 Transcription Factor D014162:Transfection D014517:Ureteral Obstruction
renal fibrosis microRNA-29c extracellular matrix leukemia inhibitor factor signal transducer and activator of transcription 3