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: Ying Yu, Yumei Wang, Yangyang Niu, Lanjun Fu, Y Eugene Chin, Chen Yu
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 309 Issue 7 Pg. F595-603 (Oct 01 2015) ISSN: 1522-1466 [Electronic] United States
• PMID: 26155847 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 the American Physiological Society.

Chemical References

• Collagen Type I
• Collagen Type III
• Extracellular Matrix Proteins
• Interleukin-6
• Leukemia Inhibitory Factor
• MIRN29 microRNA, rat
• MicroRNAs
• STAT3 Transcription Factor
• Angiotensin II

Topics

• Angiotensin II (pharmacology)
• Animals
• Cells, Cultured
• Collagen Type I (biosynthesis)
• Collagen Type III (biosynthesis)
• Computational Biology
• Extracellular Matrix Proteins (biosynthesis)
• Fibrosis
• Gene Knockdown Techniques
• Interleukin-6 (metabolism)
• Kidney (pathology)
• Kidney Diseases (drug therapy, pathology)
• Leukemia Inhibitory Factor (therapeutic use)
• Mice
• MicroRNAs (genetics)
• Nephritis, Interstitial (pathology)
• Rats
• STAT3 Transcription Factor (genetics)
• Transfection
• Ureteral Obstruction (pathology)