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Updated: Feb 23, 2026
Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration
Published on: June 7, 2014
Farnesoid X receptor activation protects the kidney from ischemia-reperfusion damage
Zhibo Gai1, Lei Chu2, Zhenqiang Xu3
1Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Abstract:
Farnesoid X receptor (FXR) activation has been reported to reduce inflammation and oxidative stress. Because both inflammation and oxidative stress are critical for tissue destruction during kidney ischemia reperfusion (I/R) injury, we investigated the protective role of FXR against kidney damage induced by I/R in mice. Mice undergoing renal I/R developed the typical features of acute kidney injury (AKI): increased creatinine, albuminuria, tubular necrosis and apoptosis. Inflammatory cytokine production and oxidative stress were also markedly increased. In mice pretreated with 6-ethyl-chenodeoxycholic acid (6-ECDCA), a selective FXR agonist, I/R induced changes were prevented and renal function and structure were improved. Moreover, FXR activation also effectively prevented the subsequent progression of AKI to chronic kidney disease (CKD) by ameliorating glomerulosclerosis and interstitial fibrosis and by suppressing fibrogenic gene expression. FXR mRNA levels were inversely correlated with the progression to CKD in mice and with the degree of interstitial fibrosis in human biopsies. In further experiments administering 6-ECDCA to renal proximal tubular cells cultured under hypoxia, the renoprotective effects of FXR activation were associated with inhibition of oxidative and ER stress and with increased antioxidant activity. In conclusion, FXR agonists may have a therapeutic role in conditions associated with ischemic kidney damage.
Insights
Farnesoid X receptor (FXR) activation protects kidneys from ischemia reperfusion (I/R) injury by reducing inflammation and oxidative stress. FXR agonists may offer a therapeutic strategy for preventing acute kidney injury and its progression to chronic kidney disease.
Area of Science:
- Nephrology
- Molecular Biology
- Pharmacology
Background:
- Kidney ischemia reperfusion (I/R) injury causes acute kidney injury (AKI) through inflammation and oxidative stress.
- Farnesoid X receptor (FXR) is known to reduce inflammation and oxidative stress.
- The protective role of FXR in kidney I/R injury requires further investigation.
Purpose of the Study:
- To investigate the protective effect of FXR activation against kidney damage induced by I/R.
- To evaluate the potential of FXR agonists in preventing AKI progression to chronic kidney disease (CKD).
Main Methods:
- Mice underwent renal I/R injury with and without pretreatment with a selective FXR agonist (6-ethyl-chenodeoxycholic acid, 6-ECDCA).
- Renal function, structure, inflammation, and oxidative stress markers were assessed.
- In vitro studies used cultured renal proximal tubular cells under hypoxia.
Main Results:
- FXR activation with 6-ECDCA significantly improved renal function and structure, reducing tubular necrosis and apoptosis in I/R-injured kidneys.
- FXR activation ameliorated glomerulosclerosis and interstitial fibrosis, suppressing fibrogenic gene expression, thereby preventing AKI progression to CKD.
- FXR mRNA levels correlated inversely with CKD progression in mice and interstitial fibrosis in human biopsies.
- In vitro, 6-ECDCA inhibited oxidative and ER stress and increased antioxidant activity in renal cells.
Conclusions:
- FXR activation demonstrates significant renoprotective effects against I/R injury and subsequent CKD progression.
- FXR agonists may represent a novel therapeutic approach for ischemic kidney damage and related conditions.
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