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Nat Commun. 2019 Oct 9;10(1):4589. doi: 10.1038/s41467-019-12332-0.

Pparg promotes differentiation and regulates mitochondrial gene expression in bladder epithelial cells.

Author information

1
Department of Urology, Genetics, and Devlopment, Pathology and Cell Biology and CSCI, Columbia University, New York, NY, 10032, USA.
2
Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.
3
Division of Developmental Biology, Cincinnati Children's Medical Center, Cincinnati, OH, USA.
4
Department of Psychiatry and Neurology, Columbia University, New York, NY, 10032, USA.
5
Department of Surgery, Ascension/St. John Providence, 16001 West Nine Mile Road, Southfield, MI, 48075, USA.
6
College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
7
Department of Genetics and Development, Columbia University, New York, NY, 10032, USA.
8
Department of Systems Biology, Columbia University, New York, NY, 10032, USA.
9
Department of Urology, Genetics, and Devlopment, Pathology and Cell Biology and CSCI, Columbia University, New York, NY, 10032, USA. clm20@cumc.columbia.edu.

Abstract

The urothelium is an epithelial barrier lining the bladder that protects against infection, fluid exchange and damage from toxins. The nuclear receptor Pparg promotes urothelial differentiation in vitro, and Pparg mutations are associated with bladder cancer. However, the function of Pparg in the healthy urothelium is unknown. Here we show that Pparg is critical in urothelial cells for mitochondrial biogenesis, cellular differentiation and regulation of inflammation in response to urinary tract infection (UTI). Superficial cells, which are critical for maintaining the urothelial barrier, fail to mature in Pparg mutants and basal cells undergo squamous-like differentiation. Pparg mutants display persistent inflammation after UTI, and Nf-KB, which is transiently activated in response to infection in the wild type urothelium, persists for months. Our observations suggest that in addition to its known roles in adipogegnesis and macrophage differentiation, that Pparg-dependent transcription plays a role in the urothelium controlling mitochondrial function development and regeneration.

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