Preventing Engrailed-1 activation in fibroblasts yields wound regeneration without scarring.
Science
; 372(6540)2021 04 23.
Article
em En
| MEDLINE
| ID: mdl-33888614
ABSTRACT
Skin scarring, the end result of adult wound healing, is detrimental to tissue form and function. Engrailed-1 lineage-positive fibroblasts (EPFs) are known to function in scarring, but Engrailed-1 lineage-negative fibroblasts (ENFs) remain poorly characterized. Using cell transplantation and transgenic mouse models, we identified a dermal ENF subpopulation that gives rise to postnatally derived EPFs by activating Engrailed-1 expression during adult wound healing. By studying ENF responses to substrate mechanics, we found that mechanical tension drives Engrailed-1 activation via canonical mechanotransduction signaling. Finally, we showed that blocking mechanotransduction signaling with either verteporfin, an inhibitor of Yes-associated protein (YAP), or fibroblast-specific transgenic YAP knockout prevents Engrailed-1 activation and promotes wound regeneration by ENFs, with recovery of skin appendages, ultrastructure, and mechanical strength. This finding suggests that there are two possible outcomes to postnatal wound healing a fibrotic response (EPF-mediated) and a regenerative response (ENF-mediated).
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regeneração
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Pele
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Cicatrização
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Cicatriz
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Proteínas de Homeodomínio
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Fibroblastos
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article