Amniotic fluid activates the nrf2/keap1 pathway to repair an epidermal barrier defect in utero.
Dev Cell
; 23(6): 1238-46, 2012 Dec 11.
Article
em En
| MEDLINE
| ID: mdl-23237955
The loss of loricrin, a major component of the cornified envelope, results in a delay of epidermal barrier formation. Therefore, the living layers of the epidermis are aberrantly exposed to late-stage amniotic fluid, which may serve as the signal to upregulate genes that functionally compensate for the loss of loricrin. Consistent with this hypothesis, metabolomic studies revealed marked changes in amniotic fluid between E14.5 and E16.5 days postcoitum. In addition, we discovered that the Nrf2/Keap1 pathway detects these compositional changes and directly upregulates the expression of genes involved in the compensatory response, thus ensuring postnatal survival. In support of this finding, we demonstrate that genetically blocking the Nrf2 pathway abolishes the compensatory response and that preemptively activating Nrf2 pharmacologically rescues the delay in barrier formation in utero. Our findings reveal that the functions of Nrf2 and the composition of amniotic fluid have coevolved to ensure the formation of a functional barrier.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Queratinócitos
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Regulação da Expressão Gênica no Desenvolvimento
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Proteínas do Citoesqueleto
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Proteínas Adaptadoras de Transdução de Sinal
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Epiderme
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Fator 2 Relacionado a NF-E2
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Líquido Amniótico
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Proteínas de Membrana
Limite:
Animals
Idioma:
En
Revista:
Dev Cell
Assunto da revista:
EMBRIOLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos