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Irisin reverses intestinal epithelial barrier dysfunction during intestinal injury via binding to the integrin αVβ5 receptor

Disruption of the gut barrier results in severe clinical outcomes with no specific treatment. Metabolic disorders and destruction of enterocytes play key roles in gut barrier dysfunction. Irisin is a newly identified exercise hormone that regulates energy metabolism. However, the effect of irisin on...

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Autores principales: Bi, Jianbin, Zhang, Jia, Ren, Yifan, Du, Zhaoqing, Li, Teng, Wang, Tao, Zhang, Lin, Wang, Mengzhou, Wu, Zheng, Lv, Yi, Wu, Rongqian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933384/
https://www.ncbi.nlm.nih.gov/pubmed/31701659
http://dx.doi.org/10.1111/jcmm.14811
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author Bi, Jianbin
Zhang, Jia
Ren, Yifan
Du, Zhaoqing
Li, Teng
Wang, Tao
Zhang, Lin
Wang, Mengzhou
Wu, Zheng
Lv, Yi
Wu, Rongqian
author_facet Bi, Jianbin
Zhang, Jia
Ren, Yifan
Du, Zhaoqing
Li, Teng
Wang, Tao
Zhang, Lin
Wang, Mengzhou
Wu, Zheng
Lv, Yi
Wu, Rongqian
author_sort Bi, Jianbin
collection PubMed
description Disruption of the gut barrier results in severe clinical outcomes with no specific treatment. Metabolic disorders and destruction of enterocytes play key roles in gut barrier dysfunction. Irisin is a newly identified exercise hormone that regulates energy metabolism. However, the effect of irisin on gut barrier function remains unknown. The therapeutic effect of irisin on gut barrier dysfunction was evaluated in gut ischemia reperfusion (IR). The direct effect of irisin on gut barrier function was studied in Caco‐2 cells. Here, we discovered that serum and gut irisin levels were decreased during gut IR and that treatment with exogenous irisin restored gut barrier function after gut IR in mice. Meanwhile, irisin decreased oxidative stress, calcium influx and endoplasmic reticulum (ER) stress after gut IR. Moreover, irisin protected mitochondrial function and reduced enterocyte apoptosis. The neutralizing antibody against irisin significantly aggravated gut injury, oxidative stress and enterocyte apoptosis after gut IR. Further studies revealed that irisin activated the AMPK‐UCP 2 pathway via binding to the integrin αVβ5 receptor. Inhibition of integrin αVβ5, AMPK or UCP 2 abolished the protective role of irisin in gut barrier function. In conclusion, exogenous irisin restores gut barrier function after gut IR via the integrin αVβ5‐AMPK‐UCP 2 pathway.
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spelling pubmed-69333842020-01-01 Irisin reverses intestinal epithelial barrier dysfunction during intestinal injury via binding to the integrin αVβ5 receptor Bi, Jianbin Zhang, Jia Ren, Yifan Du, Zhaoqing Li, Teng Wang, Tao Zhang, Lin Wang, Mengzhou Wu, Zheng Lv, Yi Wu, Rongqian J Cell Mol Med Original Articles Disruption of the gut barrier results in severe clinical outcomes with no specific treatment. Metabolic disorders and destruction of enterocytes play key roles in gut barrier dysfunction. Irisin is a newly identified exercise hormone that regulates energy metabolism. However, the effect of irisin on gut barrier function remains unknown. The therapeutic effect of irisin on gut barrier dysfunction was evaluated in gut ischemia reperfusion (IR). The direct effect of irisin on gut barrier function was studied in Caco‐2 cells. Here, we discovered that serum and gut irisin levels were decreased during gut IR and that treatment with exogenous irisin restored gut barrier function after gut IR in mice. Meanwhile, irisin decreased oxidative stress, calcium influx and endoplasmic reticulum (ER) stress after gut IR. Moreover, irisin protected mitochondrial function and reduced enterocyte apoptosis. The neutralizing antibody against irisin significantly aggravated gut injury, oxidative stress and enterocyte apoptosis after gut IR. Further studies revealed that irisin activated the AMPK‐UCP 2 pathway via binding to the integrin αVβ5 receptor. Inhibition of integrin αVβ5, AMPK or UCP 2 abolished the protective role of irisin in gut barrier function. In conclusion, exogenous irisin restores gut barrier function after gut IR via the integrin αVβ5‐AMPK‐UCP 2 pathway. John Wiley and Sons Inc. 2019-11-07 2020-01 /pmc/articles/PMC6933384/ /pubmed/31701659 http://dx.doi.org/10.1111/jcmm.14811 Text en © 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Bi, Jianbin
Zhang, Jia
Ren, Yifan
Du, Zhaoqing
Li, Teng
Wang, Tao
Zhang, Lin
Wang, Mengzhou
Wu, Zheng
Lv, Yi
Wu, Rongqian
Irisin reverses intestinal epithelial barrier dysfunction during intestinal injury via binding to the integrin αVβ5 receptor
title Irisin reverses intestinal epithelial barrier dysfunction during intestinal injury via binding to the integrin αVβ5 receptor
title_full Irisin reverses intestinal epithelial barrier dysfunction during intestinal injury via binding to the integrin αVβ5 receptor
title_fullStr Irisin reverses intestinal epithelial barrier dysfunction during intestinal injury via binding to the integrin αVβ5 receptor
title_full_unstemmed Irisin reverses intestinal epithelial barrier dysfunction during intestinal injury via binding to the integrin αVβ5 receptor
title_short Irisin reverses intestinal epithelial barrier dysfunction during intestinal injury via binding to the integrin αVβ5 receptor
title_sort irisin reverses intestinal epithelial barrier dysfunction during intestinal injury via binding to the integrin αvβ5 receptor
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933384/
https://www.ncbi.nlm.nih.gov/pubmed/31701659
http://dx.doi.org/10.1111/jcmm.14811
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