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

Author

Listed:
  • Chang Liu

    (Columbia University)

  • Tiffany Tate

    (Columbia University)

  • Ekatherina Batourina

    (Columbia University)

  • Steven T. Truschel

    (University of Pittsburgh School of Medicine)

  • Steven Potter

    (Cincinnati Children’s Medical Center)

  • Mike Adam

    (Cincinnati Children’s Medical Center)

  • Tina Xiang

    (Columbia University)

  • Martin Picard

    (Columbia University)

  • Maia Reiley

    (Columbia University
    Ascension/St. John Providence)

  • Kerry Schneider

    (Columbia University
    Cornell University)

  • Manuel Tamargo

    (Columbia University)

  • Chao Lu

    (Columbia University)

  • Xiao Chen

    (Columbia University)

  • Jing He

    (Columbia University)

  • Hyunwoo Kim

    (Columbia University)

  • Cathy Lee Mendelsohn

    (Columbia University)

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.

Suggested Citation

  • Chang Liu & Tiffany Tate & Ekatherina Batourina & Steven T. Truschel & Steven Potter & Mike Adam & Tina Xiang & Martin Picard & Maia Reiley & Kerry Schneider & Manuel Tamargo & Chao Lu & Xiao Chen & J, 2019. "Pparg promotes differentiation and regulates mitochondrial gene expression in bladder epithelial cells," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12332-0
    DOI: 10.1038/s41467-019-12332-0
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    Cited by:

    1. Tiffany Tate & Tina Xiang & Sarah E. Wobker & Mi Zhou & Xiao Chen & Hyunwoo Kim & Ekatherina Batourina & Chyuan-Sheng Lin & William Y. Kim & Chao Lu & James M. Mckiernan & Cathy Lee Mendelsohn, 2021. "Pparg signaling controls bladder cancer subtype and immune exclusion," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    2. Sakina A. Plumber & Tiffany Tate & Hikmat Al-Ahmadie & Xiao Chen & Woonyoung Choi & Merve Basar & Chao Lu & Aaron Viny & Ekatherina Batourina & Jiaqi Li & Kristjan Gretarsson & Besmira Alija & Andrei , 2024. "Rosiglitazone and trametinib exhibit potent anti-tumor activity in a mouse model of muscle invasive bladder cancer," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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