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: Siles Mena, Laura, Ninfali, Chiara, Cortés, Marlies, Darling, Douglas S., Postigo, Antonio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/169871
Acceso en línea:https://hdl.handle.net/2445/169871
Access Level:acceso abierto
Palabra clave:Múscul estriat
Distròfia muscular
Macròfags
Striated muscle
Muscular dystrophy
Macrophages
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spelling ZEB1 protects skeletal muscle from damage and is required for its regenerationSiles Mena, LauraNinfali, ChiaraCortés, MarliesDarling, Douglas S.Postigo, AntonioMúscul estriatDistròfia muscularMacròfagsStriated muscleMuscular dystrophyMacrophagesThe 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 Group2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/169871Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1038/s41467-019-08983-8Nautre Communications, 2019, vol. 10, p. 1364https://doi.org/10.1038/s41467-019-08983-8cc by (c) Siles et al., 2019http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1698712026-05-27T06:46:51Z
dc.title.none.fl_str_mv 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
spellingShingle ZEB1 protects skeletal muscle from damage and is required for its regeneration
Siles Mena, Laura
Múscul estriat
Distròfia muscular
Macròfags
Striated muscle
Muscular dystrophy
Macrophages
title_short 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_sort ZEB1 protects skeletal muscle from damage and is required for its regeneration
dc.creator.none.fl_str_mv Siles Mena, Laura
Ninfali, Chiara
Cortés, Marlies
Darling, Douglas S.
Postigo, Antonio
author Siles Mena, Laura
author_facet Siles Mena, Laura
Ninfali, Chiara
Cortés, Marlies
Darling, Douglas S.
Postigo, Antonio
author_role author
author2 Ninfali, Chiara
Cortés, Marlies
Darling, Douglas S.
Postigo, Antonio
author2_role author
author
author
author
dc.subject.none.fl_str_mv Múscul estriat
Distròfia muscular
Macròfags
Striated muscle
Muscular dystrophy
Macrophages
topic Múscul estriat
Distròfia muscular
Macròfags
Striated muscle
Muscular dystrophy
Macrophages
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.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/169871
url https://hdl.handle.net/2445/169871
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41467-019-08983-8
Nautre Communications, 2019, vol. 10, p. 1364
https://doi.org/10.1038/s41467-019-08983-8
dc.rights.none.fl_str_mv cc by (c) Siles et al., 2019
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Siles et al., 2019
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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