Related Experiment Video
Updated: Apr 7, 2026
Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
Published on: June 15, 2016
Leukemia inhibitory factor attenuates renal fibrosis through Stat3-miR-29c
Ying Yu1, Yumei Wang2, Yangyang Niu1
1Department of Nephrology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China; and.
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.
Insights
Leukemia inhibitory factor (LIF) reduces kidney fibrosis by activating Stat3 phosphorylation, which increases microRNA-29c to suppress collagen production. This mechanism was confirmed in kidney cells and obstruction models.
Area of Science:
- Nephrology
- Molecular Biology
- Cell Biology
Background:
- Leukemia inhibitory factor (LIF), part of the IL-6 family, is known to protect against heart damage.
- Renal fibrosis is a key factor in chronic kidney disease progression.
Purpose of the Study:
- To investigate the anti-fibrotic effects of LIF on kidney tissue.
- To elucidate the molecular mechanisms underlying LIF's action in renal fibrosis.
Main Methods:
- Utilized NRK-49F rat kidney fibroblast cells and a mouse model of unilateral ureteral obstruction.
- Assessed collagen type 1 and 3 expression, Stat3 phosphorylation (Tyr705 and Ser727), and microRNA-29c levels.
- Employed Stat3 knockout cells to confirm the role of Stat3 signaling.
Main Results:
- LIF significantly inhibited angiotensin II-induced collagen type 1 and 3 expression in kidney cells and in vivo.
- LIF promoted Stat3 Tyr705 phosphorylation while inhibiting ANG II-induced phosphorylation at Tyr705 and Ser727.
- LIF's anti-fibrotic effects were dependent on Stat3 activation and led to increased microRNA-29c expression, which in turn downregulated collagen production.
Conclusions:
- LIF exerts an anti-renal fibrosis effect by activating Stat3 Tyr705 phosphorylation.
- This activation upregulates microRNA-29c, leading to the suppression of collagen type 1 and 3 expression.
- LIF represents a potential therapeutic target for managing renal fibrosis.
More Related Videos
07:15Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
10:15Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection
Published on: November 10, 2021
