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Updated: May 9, 2025
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A Murine Model of Irreversible and Reversible Unilateral Ureteric Obstruction
Published on: December 20, 2014
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PPARγ promotes urothelial remodeling during urinary tract obstruction
Mohammad El-Harakeh1, Felipe Rodriguez-Tirado1, Andrew J Hardman1
1Kidney and Urinary Tract Center, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, USA.
Experimental & Molecular Medicine
|April 30, 2025
Summary
Peroxisome proliferator-activated receptor γ (PPARγ) activation in the renal urothelium is crucial for remodeling during urinary tract obstruction (UTO). This finding highlights PPARγ
Area of Science:
- Nephrology
- Urology
- Cell Biology
Background:
- Urinary tract obstruction (UTO) can lead to chronic kidney disease.
- The renal urothelium remodels during UTO, involving uroplakin (UPK)+ cell expansion.
- Mechanisms regulating UPK expression in the renal urothelium remain unclear.
Purpose of the Study:
- Investigate the role of Peroxisome proliferator-activated receptor γ (PPARγ) in renal urothelium remodeling during UTO.
- Determine if PPARγ regulates UPK expression in the renal urothelium.
Main Methods:
- Utilized conditional deletion and activation of the Pparg gene in mice.
- Assessed UPK expression and renal parenchymal changes in response to UTO.
- Examined the effects of PPARγ modulation on urothelial remodeling.
Main Results:
- Conditional deletion of Pparg impaired UPK expression and accelerated kidney damage during UTO.
- Conditional activation of PPARγ increased UPK expression and preserved kidney parenchyma.
- PPARγ activation in UPK+ cells is critical for UTO-induced renal urothelium remodeling.
Conclusions:
- UTO-induced renal urothelial remodeling is mediated by PPARγ activation.
- PPARγ plays a protective role in the renal urothelium during UTO.
- PPARγ agonists may offer therapeutic potential for UTO-related kidney injury.
