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

Author

Listed:
  • Laura Siles

    (Department of Oncology and Hematology, IDIBAPS)

  • Chiara Ninfali

    (Department of Oncology and Hematology, IDIBAPS)

  • Marlies Cortés

    (Department of Oncology and Hematology, IDIBAPS)

  • Douglas S. Darling

    (University of Louisville)

  • Antonio Postigo

    (Department of Oncology and Hematology, IDIBAPS
    James G. Brown Cancer Center
    ICREA)

Abstract

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.

Suggested Citation

  • Laura Siles & Chiara Ninfali & Marlies Cortés & Douglas S. Darling & Antonio Postigo, 2019. "ZEB1 protects skeletal muscle from damage and is required for its regeneration," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08983-8
    DOI: 10.1038/s41467-019-08983-8
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    Cited by:

    1. M. C. Martinez-Campanario & Marlies Cortés & Alazne Moreno-Lanceta & Lu Han & Chiara Ninfali & Verónica Domínguez & María J. Andrés-Manzano & Marta Farràs & Anna Esteve-Codina & Carlos Enrich & Franci, 2023. "Atherosclerotic plaque development in mice is enhanced by myeloid ZEB1 downregulation," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

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