1. Leukemia inhibitory factor attenuates renal fibrosis through Stat3-miR-29c
- Author
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Lan-Jun Fu, Y. Eugene Chin, Ying Yu, Chen Yu, Yumei Wang, and Yangyang Niu
- Subjects
STAT3 Transcription Factor ,Physiology ,Kidney ,Transfection ,Inhibitory postsynaptic potential ,Leukemia Inhibitory Factor ,Collagen Type I ,Extracellular matrix ,Mice ,medicine ,Renal fibrosis ,Animals ,STAT3 ,Cells, Cultured ,Extracellular Matrix Proteins ,biology ,Interleukin-6 ,urogenital system ,business.industry ,Angiotensin II ,Computational Biology ,medicine.disease ,Fibrosis ,Rats ,MicroRNAs ,Leukemia ,Collagen Type III ,Gene Knockdown Techniques ,Immunology ,Myocardial cell ,biology.protein ,Cancer research ,Nephritis, Interstitial ,Kidney Diseases ,Myocardial fibrosis ,business ,Leukemia inhibitory factor ,hormones, hormone substitutes, and hormone antagonists ,Ureteral Obstruction - 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 Tyr705phosphorylation and inhibited Stat3 Tyr705and Ser727phosphorylation induced by ANG II in NRK-49F cells. Third, LIF exerted an antirenal fibrosis effect mainly through activation of Stat3 Tyr705phosphorylation 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 Tyr705phosphorylation, which upregulated microRNA-29c to suppress collagen expression.
- Published
- 2015
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