Dermal αSMA+ myofibroblasts orchestrate skin wound repair via ß1 integrin and independent of type I collagen production.
EMBO J
; 41(7): e109470, 2022 04 04.
Article
en En
| MEDLINE
| ID: mdl-35212000
ABSTRACT
Skin wound repair is essential for organismal survival and failure of which leads to non-healing wounds, a leading health issue worldwide. However, mechanistic understanding of chronic wounds remains a major challenge due to lack of appropriate genetic mouse models. αSMA+ myofibroblasts, a unique class of dermal fibroblasts, are associated with cutaneous wound healing but their precise function remains unknown. We demonstrate that genetic depletion of αSMA+ myofibroblasts leads to pleiotropic wound healing defects, including lack of reepithelialization and granulation, dampened angiogenesis, and heightened hypoxia, hallmarks of chronic non-healing wounds. Other wound-associated FAP+ and FSP1+ fibroblasts do not exhibit such dominant functions. While type I collagen (COL1) expressing cells play a role in the repair process, COL1 produced by αSMA+ myofibroblasts is surprisingly dispensable for wound repair. In contrast, we show that ß1 integrin from αSMA+ myofibroblasts, but not TGFßRII, is essential for wound healing, facilitating contractility, reepithelization, and vascularization. Collectively, our study provides evidence for the functions of myofibroblasts in ß1 integrin-mediated wound repair with potential implications for treating chronic non-healing wounds.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Cicatrización de Heridas
/
Colágeno Tipo I
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Miofibroblastos
Límite:
Animals
Idioma:
En
Revista:
EMBO J
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos