Met and Cxcr4 cooperate to protect skeletal muscle stem cells against inflammation-induced damage during regeneration

Acute skeletal muscle injury is followed by an inflammatory response, removal of damaged tissue, and the generation of new muscle fibers by resident muscle stem cells, a process well characterized in murine injury models. Inflammatory cells are needed to remove the debris at the site of injury and p...

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Autores principales:	Ines Lahmann, Joscha Griger, Jie-Shin Chen, Yao Zhang, Markus Schuelke, Carmen Birchmeier
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	skeletal muscle regeneration satellite cell muscle stem cell hgf/met cxcl12/cxcr4 inflammation Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ee7880419f6c4b54acbc3f89d562f072
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spelling	oai:doaj.org-article:ee7880419f6c4b54acbc3f89d562f0722021-11-09T13:17:14ZMet and Cxcr4 cooperate to protect skeletal muscle stem cells against inflammation-induced damage during regeneration10.7554/eLife.573562050-084Xe57356https://doaj.org/article/ee7880419f6c4b54acbc3f89d562f0722021-08-01T00:00:00Zhttps://elifesciences.org/articles/57356https://doaj.org/toc/2050-084XAcute skeletal muscle injury is followed by an inflammatory response, removal of damaged tissue, and the generation of new muscle fibers by resident muscle stem cells, a process well characterized in murine injury models. Inflammatory cells are needed to remove the debris at the site of injury and provide signals that are beneficial for repair. However, they also release chemokines, reactive oxygen species, as well as enzymes for clearance of damaged cells and fibers, which muscle stem cells have to withstand in order to regenerate the muscle. We show here that MET and CXCR4 cooperate to protect muscle stem cells against the adverse environment encountered during muscle repair. This powerful cyto-protective role was revealed by the genetic ablation of Met and Cxcr4 in muscle stem cells of mice, which resulted in severe apoptosis during early stages of regeneration. TNFα neutralizing antibodies rescued the apoptosis, indicating that TNFα provides crucial cell-death signals during muscle repair that are counteracted by MET and CXCR4. We conclude that muscle stem cells require MET and CXCR4 to protect them against the harsh inflammatory environment encountered in an acute muscle injury.Ines LahmannJoscha GrigerJie-Shin ChenYao ZhangMarkus SchuelkeCarmen BirchmeiereLife Sciences Publications Ltdarticleskeletal muscle regenerationsatellite cellmuscle stem cellhgf/metcxcl12/cxcr4inflammationMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	skeletal muscle regeneration satellite cell muscle stem cell hgf/met cxcl12/cxcr4 inflammation Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	skeletal muscle regeneration satellite cell muscle stem cell hgf/met cxcl12/cxcr4 inflammation Medicine R Science Q Biology (General) QH301-705.5 Ines Lahmann Joscha Griger Jie-Shin Chen Yao Zhang Markus Schuelke Carmen Birchmeier Met and Cxcr4 cooperate to protect skeletal muscle stem cells against inflammation-induced damage during regeneration
description	Acute skeletal muscle injury is followed by an inflammatory response, removal of damaged tissue, and the generation of new muscle fibers by resident muscle stem cells, a process well characterized in murine injury models. Inflammatory cells are needed to remove the debris at the site of injury and provide signals that are beneficial for repair. However, they also release chemokines, reactive oxygen species, as well as enzymes for clearance of damaged cells and fibers, which muscle stem cells have to withstand in order to regenerate the muscle. We show here that MET and CXCR4 cooperate to protect muscle stem cells against the adverse environment encountered during muscle repair. This powerful cyto-protective role was revealed by the genetic ablation of Met and Cxcr4 in muscle stem cells of mice, which resulted in severe apoptosis during early stages of regeneration. TNFα neutralizing antibodies rescued the apoptosis, indicating that TNFα provides crucial cell-death signals during muscle repair that are counteracted by MET and CXCR4. We conclude that muscle stem cells require MET and CXCR4 to protect them against the harsh inflammatory environment encountered in an acute muscle injury.
format	article
author	Ines Lahmann Joscha Griger Jie-Shin Chen Yao Zhang Markus Schuelke Carmen Birchmeier
author_facet	Ines Lahmann Joscha Griger Jie-Shin Chen Yao Zhang Markus Schuelke Carmen Birchmeier
author_sort	Ines Lahmann
title	Met and Cxcr4 cooperate to protect skeletal muscle stem cells against inflammation-induced damage during regeneration
title_short	Met and Cxcr4 cooperate to protect skeletal muscle stem cells against inflammation-induced damage during regeneration
title_full	Met and Cxcr4 cooperate to protect skeletal muscle stem cells against inflammation-induced damage during regeneration
title_fullStr	Met and Cxcr4 cooperate to protect skeletal muscle stem cells against inflammation-induced damage during regeneration
title_full_unstemmed	Met and Cxcr4 cooperate to protect skeletal muscle stem cells against inflammation-induced damage during regeneration
title_sort	met and cxcr4 cooperate to protect skeletal muscle stem cells against inflammation-induced damage during regeneration
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/ee7880419f6c4b54acbc3f89d562f072
work_keys_str_mv	AT ineslahmann metandcxcr4cooperatetoprotectskeletalmusclestemcellsagainstinflammationinduceddamageduringregeneration AT joschagriger metandcxcr4cooperatetoprotectskeletalmusclestemcellsagainstinflammationinduceddamageduringregeneration AT jieshinchen metandcxcr4cooperatetoprotectskeletalmusclestemcellsagainstinflammationinduceddamageduringregeneration AT yaozhang metandcxcr4cooperatetoprotectskeletalmusclestemcellsagainstinflammationinduceddamageduringregeneration AT markusschuelke metandcxcr4cooperatetoprotectskeletalmusclestemcellsagainstinflammationinduceddamageduringregeneration AT carmenbirchmeier metandcxcr4cooperatetoprotectskeletalmusclestemcellsagainstinflammationinduceddamageduringregeneration
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Met and Cxcr4 cooperate to protect skeletal muscle stem cells against inflammation-induced damage during regeneration

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