Estrogen-related receptor alpha (ERRα) is a key regulator of intestinal homeostasis and protects against colitis

Abstract The estrogen-related receptor alpha (ERRα) is a primary regulator of mitochondrial energy metabolism, function and dynamics, and has been implicated in autophagy and immune regulation. ERRα is abundantly expressed in the intestine and in cells of the immune system. However, its role in infl...

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Autores principales:	Allan Tran, Charlotte Scholtes, Mario Songane, Claudia Champagne, Luc Galarneau, Marie-Pier Levasseur, Nassima Fodil, Catherine Rosa Dufour, Vincent Giguère, Maya Saleh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/31be6f5a64804b909ef3f38b8309e70b
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spelling	oai:doaj.org-article:31be6f5a64804b909ef3f38b8309e70b2021-12-02T17:03:49ZEstrogen-related receptor alpha (ERRα) is a key regulator of intestinal homeostasis and protects against colitis10.1038/s41598-021-94499-52045-2322https://doaj.org/article/31be6f5a64804b909ef3f38b8309e70b2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94499-5https://doaj.org/toc/2045-2322Abstract The estrogen-related receptor alpha (ERRα) is a primary regulator of mitochondrial energy metabolism, function and dynamics, and has been implicated in autophagy and immune regulation. ERRα is abundantly expressed in the intestine and in cells of the immune system. However, its role in inflammatory bowel disease (IBD) remains unknown. Here, we report a protective role of ERRα in the intestine. We found that mice deficient in ERRα were susceptible to experimental colitis, exhibiting increased colon inflammation and tissue damage. This phenotype was mediated by impaired compensatory proliferation of intestinal epithelial cells (IEC) following injury, enhanced IEC apoptosis and necrosis and reduced mucus-producing goblet cell counts. Longitudinal analysis of the microbiota demonstrated that loss of ERRα lead to a reduction in microbiome α-diversity and depletion of healthy gut bacterial constituents. Mechanistically, ERRα mediated its protective effects by acting within the radio-resistant compartment of the intestine. It promoted disease tolerance through transcriptional control of key genes involved in intestinal tissue homeostasis and repair. These findings provide new insights on the role of ERRα in the gut and extends our current knowledge of nuclear receptors implicated in IBD.Allan TranCharlotte ScholtesMario SonganeClaudia ChampagneLuc GalarneauMarie-Pier LevasseurNassima FodilCatherine Rosa DufourVincent GiguèreMaya SalehNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Allan Tran Charlotte Scholtes Mario Songane Claudia Champagne Luc Galarneau Marie-Pier Levasseur Nassima Fodil Catherine Rosa Dufour Vincent Giguère Maya Saleh Estrogen-related receptor alpha (ERRα) is a key regulator of intestinal homeostasis and protects against colitis
description	Abstract The estrogen-related receptor alpha (ERRα) is a primary regulator of mitochondrial energy metabolism, function and dynamics, and has been implicated in autophagy and immune regulation. ERRα is abundantly expressed in the intestine and in cells of the immune system. However, its role in inflammatory bowel disease (IBD) remains unknown. Here, we report a protective role of ERRα in the intestine. We found that mice deficient in ERRα were susceptible to experimental colitis, exhibiting increased colon inflammation and tissue damage. This phenotype was mediated by impaired compensatory proliferation of intestinal epithelial cells (IEC) following injury, enhanced IEC apoptosis and necrosis and reduced mucus-producing goblet cell counts. Longitudinal analysis of the microbiota demonstrated that loss of ERRα lead to a reduction in microbiome α-diversity and depletion of healthy gut bacterial constituents. Mechanistically, ERRα mediated its protective effects by acting within the radio-resistant compartment of the intestine. It promoted disease tolerance through transcriptional control of key genes involved in intestinal tissue homeostasis and repair. These findings provide new insights on the role of ERRα in the gut and extends our current knowledge of nuclear receptors implicated in IBD.
format	article
author	Allan Tran Charlotte Scholtes Mario Songane Claudia Champagne Luc Galarneau Marie-Pier Levasseur Nassima Fodil Catherine Rosa Dufour Vincent Giguère Maya Saleh
author_facet	Allan Tran Charlotte Scholtes Mario Songane Claudia Champagne Luc Galarneau Marie-Pier Levasseur Nassima Fodil Catherine Rosa Dufour Vincent Giguère Maya Saleh
author_sort	Allan Tran
title	Estrogen-related receptor alpha (ERRα) is a key regulator of intestinal homeostasis and protects against colitis
title_short	Estrogen-related receptor alpha (ERRα) is a key regulator of intestinal homeostasis and protects against colitis
title_full	Estrogen-related receptor alpha (ERRα) is a key regulator of intestinal homeostasis and protects against colitis
title_fullStr	Estrogen-related receptor alpha (ERRα) is a key regulator of intestinal homeostasis and protects against colitis
title_full_unstemmed	Estrogen-related receptor alpha (ERRα) is a key regulator of intestinal homeostasis and protects against colitis
title_sort	estrogen-related receptor alpha (errα) is a key regulator of intestinal homeostasis and protects against colitis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/31be6f5a64804b909ef3f38b8309e70b
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Estrogen-related receptor alpha (ERRα) is a key regulator of intestinal homeostasis and protects against colitis

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