FOXO1 promotes wound healing through the up-regulation of TGF-ß1 and prevention of oxidative stress.
J Cell Biol
; 203(2): 327-43, 2013 Oct 28.
Article
em En
| MEDLINE
| ID: mdl-24145170
ABSTRACT
Keratinocyte mobilization is a critical aspect of wound re-epithelialization, but the mechanisms that control its precise regulation remain poorly understood. We set out to test the hypothesis that forkhead box O1 (FOXO1) has a negative effect on healing because of its capacity to inhibit proliferation and promote apoptosis. Contrary to expectations, FOXO1 is required for keratinocyte transition to a wound-healing phenotype that involves increased migration and up-regulation of transforming growth factor ß1 (TGF-ß1) and its downstream targets, integrin-α3 and -ß6 and MMP-3 and -9. Furthermore, we show that FOXO1 functions in keratinocytes to reduce oxidative stress, which is necessary to maintain cell migration and prevent cell death in a TGF-ß1-independent manner. Thus, our studies identify a novel function for FOXO1 in coordinating the response of keratinocytes to wounding through up-regulation of TGF-ß1 and other factors needed for keratinocyte migration and protection against oxidative stress, which together promote migration and decrease apoptosis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cicatrização
/
Queratinócitos
/
Estresse Oxidativo
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Fatores de Transcrição Forkhead
/
Fator de Crescimento Transformador beta1
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article