Related Experiment Video
Updated: Aug 17, 2026
Mouse Model of Acute to Chronic Kidney Disease Transition Induced by Renal Ischemia/Reperfusion Injury
Published on: February 10, 2026
Peroxisome proliferator-activated receptor beta/delta exerts a strong protection from ischemic acute renal failure
Emmanuel Letavernier1, Joëlle Perez, Elisabeth Joye
1INSERM U489, Hôpital Tenon, 4 rue de la Chine, Paris, France 75020.
Abstract:
Ischemic acute renal failure is characterized by damages to the proximal straight tubule in the outer medulla. Lesions include loss of polarity, shedding into the tubule lumen, and eventually necrotic or apoptotic death of epithelial cells. It was recently shown that peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) increases keratinocyte survival after an inflammatory reaction. Therefore, whether PPARbeta/delta could contribute also to the control of tubular epithelium death after renal ischemia/reperfusion was tested. It was found that PPARbeta/delta+/- and PPARbeta/delta-/- mutant mice exhibited much greater kidney dysfunction and injury than wild-type counterparts after a 30-min renal ischemia followed by a 36-h reperfusion. Conversely, wild-type mice that were given the specific PPARbeta/delta ligand L-165041 before renal ischemia were completely protected against renal dysfunction, as indicated by the lack of rise in serum creatinine and fractional excretion of Na+. This protective effect was accompanied by a significant reduction in medullary necrosis, apoptosis, and inflammation. On the basis of in vitro studies, PPARbeta/delta ligands seem to exert their role by activating the antiapoptotic Akt signaling pathway and, unexpectedly, by increasing the spreading of tubular epithelial cells, thus limiting potentially their shedding and anoikis. These results point to PPARbeta/delta as a remarkable new target for preconditioning strategies.
Insights
Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) protects kidneys from ischemic injury. Activating PPARbeta/delta in wild-type mice prevented kidney dysfunction and cell death after ischemia/reperfusion.
Area of Science:
- Nephrology
- Molecular Biology
- Cell Biology
Background:
- Ischemic acute renal failure causes proximal tubule damage, including cell death.
- Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) promotes keratinocyte survival during inflammation.
Purpose of the Study:
- To investigate the role of PPARbeta/delta in protecting tubular epithelial cells from ischemia/reperfusion injury.
- To determine if PPARbeta/delta activation can prevent kidney dysfunction after renal ischemia.
Main Methods:
- Comparison of kidney injury in wild-type, PPARbeta/delta+/- and PPARbeta/delta-/- mutant mice after ischemia/reperfusion.
- Administration of a PPARbeta/delta ligand (L-165041) to wild-type mice before ischemia.
- Assessment of renal dysfunction via serum creatinine and fractional excretion of Na+.
- Histological analysis of kidney tissue for necrosis, apoptosis, and inflammation.
- In vitro studies to elucidate the molecular mechanisms of PPARbeta/delta action.
Main Results:
- PPARbeta/delta mutant mice showed significantly increased kidney dysfunction and injury compared to wild-type mice.
- Pre-treatment with L-165041 completely protected wild-type mice from renal dysfunction and injury.
- PPARbeta/delta activation reduced medullary necrosis, apoptosis, and inflammation.
- In vitro studies indicated PPARbeta/delta ligands activate the antiapoptotic Akt pathway and promote tubular epithelial cell spreading.
Conclusions:
- PPARbeta/delta plays a crucial protective role in the kidney against ischemia/reperfusion injury.
- PPARbeta/delta ligands represent a promising therapeutic target for preconditioning strategies to prevent acute renal failure.
Related Concept Videos
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
01:29Acute Kidney Injury II: Pathophysiology