Pparg promotes differentiation and regulates mitochondrial gene expression in bladder epithelial cells
| Autor: | Martin Picard, Xiao Chen, Maia Reiley, Jing He, S. Steven Potter, Kerry Schneider, Cathy Mendelsohn, Manuel A. Tamargo, Hyunwoo Kim, Tiffany Tate, Mike Adam, Chao Lu, Chang Liu, Ekatherina Batourina, Steven T. Truschel, Tina Xiang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
endocrine system diseases Cellular differentiation Organogenesis General Physics and Astronomy Peroxisome proliferator-activated receptor Gene Expression urologic and male genital diseases 0302 clinical medicine Gene expression lcsh:Science chemistry.chemical_classification Mice Knockout Multidisciplinary Cell Differentiation female genital diseases and pregnancy complications 3. Good health Genes Mitochondrial 030220 oncology & carcinogenesis Differentiation Urinary Tract Infections medicine.symptom Peroxisome proliferator-activated receptor gamma Science Urinary Bladder Inflammation Mice Transgenic Biology General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences medicine Animals Humans Urothelium nutritional and metabolic diseases Epithelial Cells General Chemistry PPAR gamma 030104 developmental biology chemistry Nuclear receptor Mitochondrial biogenesis Urinary Bladder Neoplasms Mutation Cancer research lcsh:Q |
| Zdroj: | Nature Communications Nature Communications, Vol 10, Iss 1, Pp 1-16 (2019) |
| ISSN: | 2041-1723 |
| Popis: | 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. The nuclear receptor Pparg regulates urothelial differentiation in vitro but its role in healthy urothelium is unclear. Here, the authors show that PPAR gamma mediates urothelial development during both homeostasis (via mitochondrial function) and following infection, via an inflammatory response. |
| Databáze: | OpenAIRE |
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