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Leukemia inhibitory factor attenuates renal fibrosis through Stat3-miR-29c
- Source :
- American Journal of Physiology-Renal Physiology. 309:F595-F603
- Publication Year :
- 2015
- Publisher :
- American Physiological Society, 2015.
-
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.
- 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
Subjects
Details
- ISSN :
- 15221466 and 1931857X
- Volume :
- 309
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Renal Physiology
- Accession number :
- edsair.doi.dedup.....2bf59f5ac2d34231a47e48a1007a0774
- Full Text :
- https://doi.org/10.1152/ajprenal.00634.2014