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Pparg promotes differentiation and regulates mitochondrial gene expression in bladder epithelial cells
Chang Liu1, Tiffany Tate1, Ekatherina Batourina1
1Department of Urology, Genetics, and Devlopment, Pathology and Cell Biology and CSCI, Columbia University, New York, NY, 10032, USA.
Nature Communications
|October 11, 2019
Summary
The nuclear receptor PPARG is essential for bladder urothelial health, controlling cell differentiation and inflammation. PPARG deficiency impairs barrier function and leads to chronic inflammation after urinary tract infections.
Area of Science:
- Urothelial biology
- Molecular mechanisms of inflammation
- Nuclear receptor signaling
Background:
- The urothelium forms a protective barrier in the bladder.
- PPARG (peroxisome proliferator-activated receptor gamma) is known to promote urothelial differentiation in vitro.
- PPARG mutations are linked to bladder cancer, but its role in healthy urothelium is unclear.
Purpose of the Study:
- To investigate the function of PPARG in the healthy urothelium.
- To understand PPARG's role in urothelial response to urinary tract infection (UTI).
Main Methods:
- Analysis of PPARG function in urothelial cells.
- Investigating mitochondrial biogenesis and cellular differentiation.
- Assessing inflammatory responses post-UTI in PPARG mutants.
Main Results:
- PPARG is critical for urothelial mitochondrial biogenesis, differentiation, and inflammation regulation.
- PPARG deficiency leads to impaired superficial cell maturation and squamous-like differentiation of basal cells.
- PPARG mutants exhibit persistent inflammation and prolonged NF-κB activation after UTI.
Conclusions:
- PPARG plays a crucial role in urothelial development, regeneration, and immune response.
- PPARG-dependent transcription is vital for maintaining bladder barrier integrity and controlling inflammation.
- Findings suggest novel roles for PPARG in urothelial mitochondrial function and repair.
