Related Experiment Video
Updated: Dec 31, 2025
Unilateral Ureteral Obstruction Model for Investigating Kidney Interstitial Fibrosis
Published on: April 25, 2025
Ruxolitinib Alleviates Renal Interstitial Fibrosis in UUO Mice
Yu Bai1,2, Wei Wang1, Ping Yin1
1Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, China.
Abstract:
Ruxolitinib is a selective inhibitor of Jak1/2. Downstream signaling pathways of Jak, such as Stat3 and Akt/mTOR, are overactivated and contribute to renal interstitial fibrosis. Therefore, we explored the effect of Ruxolitinib on this pathological process. Unilateral ureteral obstruction (UUO) models and TGF-β1-treated fibroblasts and renal tubular epithelial cells were adopted in this study. Ruxolitinib was administered to UUO mice and TGF-β1-treated cells. Kidneys from UUO mice with Ruxolitinib treatment displayed less tubular injuries compared with those without Ruxolitinib treatment. Ruxolitinib treatment suppressed fibroblast activation and extracellular matrix (ECM) production in UUO kidneys and TGF-β1-treated fibroblasts. Ruxolitinib treatment also blocked epithelial-mesenchymal transition (EMT) in UUO kidneys and TGF-β 1-treated renal tubular epithelial cells. Moreover, Ruxolitinib treatment alleviated UUO-induced inflammation, oxidative stress and apoptosis. Mechanistically, Ruxolitinib treatment attenuated activation of both Stat3 and Akt/mTOR/Yap pathways. In conclusion, Ruxolitinib treatment can ameliorate UUO-induced renal interstitial fibrosis, suggesting that Ruxolitinib may be potentially used to treat fibrotic kidney disease.
Insights
Ruxolitinib, a Jak1/2 inhibitor, reduces kidney fibrosis by blocking inflammation and cell damage. This study suggests its potential for treating fibrotic kidney disease.
Area of Science:
- Nephrology
- Pharmacology
- Cell Biology
Background:
- Renal interstitial fibrosis is driven by overactivated Janus kinase (Jak) signaling pathways, including Stat3 and Akt/mTOR.
- These pathways contribute to pathological processes in fibrotic kidney disease.
Purpose of the Study:
- To investigate the therapeutic potential of Ruxolitinib, a selective Jak1/2 inhibitor, in ameliorating renal interstitial fibrosis.
- To explore the effects of Ruxolitinib on cellular signaling pathways involved in kidney fibrosis.
Main Methods:
- Utilized unilateral ureteral obstruction (UUO) mouse models and transforming growth factor-beta 1 (TGF-β1)-treated renal cells (fibroblasts and tubular epithelial cells).
- Administered Ruxolitinib to UUO mice and TGF-β1-treated cells to assess its impact on fibrosis markers and signaling pathways.
Main Results:
- Ruxolitinib treatment significantly reduced tubular injury, inflammation, oxidative stress, and apoptosis in UUO kidneys.
- Ruxolitinib suppressed fibroblast activation, extracellular matrix (ECM) production, and epithelial-mesenchymal transition (EMT) in both in vivo and in vitro models.
- Mechanistically, Ruxolitinib attenuated the activation of Stat3 and Akt/mTOR/Yap signaling pathways.
Conclusions:
- Ruxolitinib effectively ameliorates unilateral ureteral obstruction-induced renal interstitial fibrosis.
- The findings suggest Ruxolitinib holds promise as a potential therapeutic agent for treating fibrotic kidney diseases.
