ZEB1 protects skeletal muscle from damage and is required for its regeneration

The mechanisms linking muscle injury and regeneration are not fully understood. Here we report an unexpected role for ZEB1 regulating inflammatory and repair responses in dystrophic and acutely injured muscles. ZEB1 is upregulated in the undamaged and regenerating myofibers of injured muscles. Compa...

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Autores principales: Siles, Laura, Ninfali, Chiara, Cortés, Marlies, Darling, Douglas S., Postigo, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434033/
https://www.ncbi.nlm.nih.gov/pubmed/30910999
http://dx.doi.org/10.1038/s41467-019-08983-8
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author Siles, Laura
Ninfali, Chiara
Cortés, Marlies
Darling, Douglas S.
Postigo, Antonio
author_facet Siles, Laura
Ninfali, Chiara
Cortés, Marlies
Darling, Douglas S.
Postigo, Antonio
author_sort Siles, Laura
collection PubMed
description The mechanisms linking muscle injury and regeneration are not fully understood. Here we report an unexpected role for ZEB1 regulating inflammatory and repair responses in dystrophic and acutely injured muscles. ZEB1 is upregulated in the undamaged and regenerating myofibers of injured muscles. Compared to wild-type counterparts, Zeb1-deficient injured muscles exhibit enhanced damage that corresponds with a retarded p38-MAPK-dependent transition of their macrophages towards an anti-inflammatory phenotype. Zeb1-deficient injured muscles also display a delayed and poorer regeneration that is accounted by the retarded anti-inflammatory macrophage transition and their intrinsically deficient muscle satellite cells (MuSCs). Macrophages in Zeb1-deficient injured muscles show lower phosphorylation of p38 and its forced activation reverts the enhanced muscle damage and poorer regeneration. MuSCs require ZEB1 to maintain their quiescence, prevent their premature activation following injury, and drive efficient regeneration in dystrophic muscles. These data indicate that ZEB1 protects muscle from damage and is required for its regeneration.
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spelling pubmed-64340332019-03-27 ZEB1 protects skeletal muscle from damage and is required for its regeneration Siles, Laura Ninfali, Chiara Cortés, Marlies Darling, Douglas S. Postigo, Antonio Nat Commun Article The mechanisms linking muscle injury and regeneration are not fully understood. Here we report an unexpected role for ZEB1 regulating inflammatory and repair responses in dystrophic and acutely injured muscles. ZEB1 is upregulated in the undamaged and regenerating myofibers of injured muscles. Compared to wild-type counterparts, Zeb1-deficient injured muscles exhibit enhanced damage that corresponds with a retarded p38-MAPK-dependent transition of their macrophages towards an anti-inflammatory phenotype. Zeb1-deficient injured muscles also display a delayed and poorer regeneration that is accounted by the retarded anti-inflammatory macrophage transition and their intrinsically deficient muscle satellite cells (MuSCs). Macrophages in Zeb1-deficient injured muscles show lower phosphorylation of p38 and its forced activation reverts the enhanced muscle damage and poorer regeneration. MuSCs require ZEB1 to maintain their quiescence, prevent their premature activation following injury, and drive efficient regeneration in dystrophic muscles. These data indicate that ZEB1 protects muscle from damage and is required for its regeneration. Nature Publishing Group UK 2019-03-25 /pmc/articles/PMC6434033/ /pubmed/30910999 http://dx.doi.org/10.1038/s41467-019-08983-8 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Siles, Laura
Ninfali, Chiara
Cortés, Marlies
Darling, Douglas S.
Postigo, Antonio
ZEB1 protects skeletal muscle from damage and is required for its regeneration
title ZEB1 protects skeletal muscle from damage and is required for its regeneration
title_full ZEB1 protects skeletal muscle from damage and is required for its regeneration
title_fullStr ZEB1 protects skeletal muscle from damage and is required for its regeneration
title_full_unstemmed ZEB1 protects skeletal muscle from damage and is required for its regeneration
title_short ZEB1 protects skeletal muscle from damage and is required for its regeneration
title_sort zeb1 protects skeletal muscle from damage and is required for its regeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434033/
https://www.ncbi.nlm.nih.gov/pubmed/30910999
http://dx.doi.org/10.1038/s41467-019-08983-8
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