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Updated: Oct 17, 2025
Ischemia-reperfusion Model of Acute Kidney Injury and Post Injury Fibrosis in Mice
Published on: August 9, 2013
Gremlin1 and TGF-β1 protect kidney tubular epithelial cells from ischemia-reperfusion injury through different
Xuxia Gao1, Liyuan Han2, Xinbao Yao3
1Department of General Internal Medicine, Beijing Anzhen Hospital, Capital Medical University, 2 Anzhen Road, Chao Yang District, Beijing, 100029, People's Republic of China. xuxiag@ccmu.edu.cn.
Background:
Gremlin1 belongs to the superfamily members of transforming growth factor (TGF)-β1, playing a profibrotic role in chronic kidney diseases (CKD) and the transition from the late stage of acute kidney injury (AKI) to CKD, but the effect it plays in the early stage of AKI is unclear. This study aimed to investigate the role of Gremlin1on apoptosis in renal tubular epithelial cells under ischemia-reperfusion (I/R) induction.
Methods:
We detected Gremlin1 and TGF-β1 expression in the kidneys of mice undergoing renal ischemia-reperfusion injury bilaterally. We induced apoptosis through depletion and reperfusion of oxygen and serum in human kidney tubular epithelial cells (HKCs), mimicking I/R injury in vivo, and detected the role and pathways of Gremlin1 and TGF-β1on HKCs injury.
Results:
Mice undergoing bilateral I/R surgery presented AKI with a significant increase in serum creatinine, obvious renal tubular injuries, and increased macrophage cell and T-cell infiltration in interstitial areas. Gremlin1 expression was significantly increased along with TGF-β1 in the kidneys of AKI mice compared to sham mice. Exogenous Gremlin1 inhibited I/R-induced caspase3 expression in HKCs, which was blocked by a VEGFR2 kinase inhibitor III (SU5416). TGF-β1 also inhibited I/R-induced cell apoptosis in HKCs but had no synergic effect with Gremlin1. The TGF-β1's inhibitory effect could be blocked by the TGF-β1 type I receptor (activin receptor-like kinase 5, and ALK5)-specific inhibitor SB431542.
Conclusions:
Gremlin1 and TGF- β1 protect kidney tubular epithelial cells from ischemia-reperfusion-induced apoptosis through VEGFR2 and Smad2 signaling pathways.
Insights
Gremlin1 and TGF-β1 protect kidney cells from injury during ischemia-reperfusion. These factors reduce apoptosis via VEGFR2 and Smad2 pathways, offering potential therapeutic targets for acute kidney injury.
Area of Science:
- Nephrology
- Cell Biology
- Molecular Biology
Background:
- Gremlin1, a TGF-β1 superfamily member, is implicated in kidney fibrosis.
- Its role in early acute kidney injury (AKI) remains unclear.
- This study investigates Gremlin1's effect on renal tubular cell apoptosis during ischemia-reperfusion (I/R).
Purpose of the Study:
- To elucidate the role of Gremlin1 in renal tubular epithelial cell apoptosis following I/R injury.
- To investigate the underlying molecular pathways involved.
Main Methods:
- Assessed Gremlin1 and TGF-β1 expression in AKI mouse kidneys.
- Induced I/R injury in human kidney tubular cells (HKCs) in vitro.
- Examined the effects of Gremlin1 and TGF-β1 on HKC apoptosis and signaling pathways.
Main Results:
- I/R injury in mice led to AKI markers, tubular damage, and immune cell infiltration.
- Gremlin1 and TGF-β1 expression increased in AKI kidneys.
- Exogenous Gremlin1 and TGF-β1 inhibited I/R-induced HKC apoptosis.
- Gremlin1's effect was mediated by VEGFR2; TGF-β1's by ALK5.
Conclusions:
- Gremlin1 and TGF-β1 exhibit protective effects on kidney tubular cells against I/R-induced apoptosis.
- These protective mechanisms involve the VEGFR2 and Smad2 signaling pathways.
- Findings suggest potential therapeutic strategies for AKI targeting these pathways.
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