The IRE1/XBP1 signaling axis promotes skeletal muscle regeneration through a cell non-autonomous mechanism

Skeletal muscle regeneration is regulated by coordinated activation of multiple signaling pathways. The unfolded protein response (UPR) is a major mechanism that detects and alleviates protein-folding stresses in the endoplasmic reticulum. However, the role of individual arms of the UPR in skeletal...

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Autores principales:	Anirban Roy, Meiricris Tomaz da Silva, Raksha Bhat, Kyle R Bohnert, Takao Iwawaki, Ashok Kumar
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	skeletal muscle regeneration ER stress satellite cells ire1 signaling XBP1 Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/213f2e124a034514a52409f257c44e19
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spelling	oai:doaj.org-article:213f2e124a034514a52409f257c44e192021-12-01T15:46:37ZThe IRE1/XBP1 signaling axis promotes skeletal muscle regeneration through a cell non-autonomous mechanism10.7554/eLife.732152050-084Xe73215https://doaj.org/article/213f2e124a034514a52409f257c44e192021-11-01T00:00:00Zhttps://elifesciences.org/articles/73215https://doaj.org/toc/2050-084XSkeletal muscle regeneration is regulated by coordinated activation of multiple signaling pathways. The unfolded protein response (UPR) is a major mechanism that detects and alleviates protein-folding stresses in the endoplasmic reticulum. However, the role of individual arms of the UPR in skeletal muscle regeneration remain less understood. In the present study, we demonstrate that IRE1α (also known as ERN1) and its downstream target, XBP1, are activated in skeletal muscle of mice upon injury. Myofiber-specific ablation of IRE1α or XBP1 in mice diminishes skeletal muscle regeneration that is accompanied with reduced number of satellite cells. Ex vivo cultures of myofiber explants demonstrate that ablation of IRE1α reduces the proliferative capacity of myofiber-associated satellite cells. Myofiber-specific ablation of IRE1α dampens Notch signaling and canonical NF-κB pathway in skeletal muscle of adult mice. Finally, targeted ablation of IRE1α also reduces Notch signaling, abundance of satellite cells, and skeletal muscle regeneration in the mdx mice, a model of Duchenne muscular dystrophy. Collectively, our experiments suggest that the IRE1α-mediated signaling promotes muscle regeneration through augmenting the proliferation of satellite cells in a cell non-autonomous manner.Anirban RoyMeiricris Tomaz da SilvaRaksha BhatKyle R BohnertTakao IwawakiAshok KumareLife Sciences Publications Ltdarticleskeletal muscleregenerationER stresssatellite cellsire1 signalingXBP1MedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	skeletal muscle regeneration ER stress satellite cells ire1 signaling XBP1 Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	skeletal muscle regeneration ER stress satellite cells ire1 signaling XBP1 Medicine R Science Q Biology (General) QH301-705.5 Anirban Roy Meiricris Tomaz da Silva Raksha Bhat Kyle R Bohnert Takao Iwawaki Ashok Kumar The IRE1/XBP1 signaling axis promotes skeletal muscle regeneration through a cell non-autonomous mechanism
description	Skeletal muscle regeneration is regulated by coordinated activation of multiple signaling pathways. The unfolded protein response (UPR) is a major mechanism that detects and alleviates protein-folding stresses in the endoplasmic reticulum. However, the role of individual arms of the UPR in skeletal muscle regeneration remain less understood. In the present study, we demonstrate that IRE1α (also known as ERN1) and its downstream target, XBP1, are activated in skeletal muscle of mice upon injury. Myofiber-specific ablation of IRE1α or XBP1 in mice diminishes skeletal muscle regeneration that is accompanied with reduced number of satellite cells. Ex vivo cultures of myofiber explants demonstrate that ablation of IRE1α reduces the proliferative capacity of myofiber-associated satellite cells. Myofiber-specific ablation of IRE1α dampens Notch signaling and canonical NF-κB pathway in skeletal muscle of adult mice. Finally, targeted ablation of IRE1α also reduces Notch signaling, abundance of satellite cells, and skeletal muscle regeneration in the mdx mice, a model of Duchenne muscular dystrophy. Collectively, our experiments suggest that the IRE1α-mediated signaling promotes muscle regeneration through augmenting the proliferation of satellite cells in a cell non-autonomous manner.
format	article
author	Anirban Roy Meiricris Tomaz da Silva Raksha Bhat Kyle R Bohnert Takao Iwawaki Ashok Kumar
author_facet	Anirban Roy Meiricris Tomaz da Silva Raksha Bhat Kyle R Bohnert Takao Iwawaki Ashok Kumar
author_sort	Anirban Roy
title	The IRE1/XBP1 signaling axis promotes skeletal muscle regeneration through a cell non-autonomous mechanism
title_short	The IRE1/XBP1 signaling axis promotes skeletal muscle regeneration through a cell non-autonomous mechanism
title_full	The IRE1/XBP1 signaling axis promotes skeletal muscle regeneration through a cell non-autonomous mechanism
title_fullStr	The IRE1/XBP1 signaling axis promotes skeletal muscle regeneration through a cell non-autonomous mechanism
title_full_unstemmed	The IRE1/XBP1 signaling axis promotes skeletal muscle regeneration through a cell non-autonomous mechanism
title_sort	ire1/xbp1 signaling axis promotes skeletal muscle regeneration through a cell non-autonomous mechanism
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/213f2e124a034514a52409f257c44e19
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The IRE1/XBP1 signaling axis promotes skeletal muscle regeneration through a cell non-autonomous mechanism

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