Met and Cxcr4 cooperate to protect skeletal muscle stem cells against inflammation-induced damage during regeneration
- Max Delbrück Center for Molecular Medicine in the Helmholtz Society, Germany
- Max Delbrueck Center for Molecular Medicine (MDC) in the Helmholtz Society, Germany
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany, Germany
Abstract
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.
Data availability
Data are available in the Article, Supplementary Information or from the corresponding authors (CB) upon reasonable request. Source data are provided with this paper.
Article and author information
Author details
Carmen Birchmeier-Kohler
Funding
Deutsche Forschungsgemeinschaft
- Carmen Birchmeier-Kohler
AFM
- Carmen Birchmeier-Kohler
Klinische Forschergruppe KFO 192
- Carmen Birchmeier-Kohler
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Gabrielle Kardon, University of Utah, United States
Ethics
Animal experimentation: All experiments were conducted according to regulations established by the Max-Delbrück- Center for Molecular Medicine (MDC) and the Landesamt für Gesundheit und Soziales (0320/10; 0130/13).
Version history
- Received: March 29, 2020
- Accepted: August 4, 2021
- Accepted Manuscript published: August 5, 2021 (version 1)
- Version of Record published: August 17, 2021 (version 2)
- Version of Record updated: August 18, 2021 (version 3)
Copyright
© 2021, Lahmann et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Met and Cxcr4 cooperate to protect skeletal muscle stem cells against inflammation-induced damage during regeneration
eLife 10:e57356.
https://doi.org/10.7554/eLife.57356
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