Nrf2 links epidermal barrier function with antioxidant defense.

Détails

Ressource 1Télécharger: BIB_814919DBD5B5.P001.pdf (1383.87 [Ko])
Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_814919DBD5B5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Nrf2 links epidermal barrier function with antioxidant defense.
Périodique
EMBO Molecular Medicine
Auteur(s)
Schäfer M., Farwanah H., Willrodt A.H., Huebner A.J., Sandhoff K., Roop D., Hohl D., Bloch W., Werner S.
ISSN
1757-4684 (Electronic)
ISSN-L
1757-4676
Statut éditorial
Publié
Date de publication
2012
Volume
4
Numéro
5
Pages
364-379
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Résumé
The skin provides an efficient permeability barrier and protects from microbial invasion and oxidative stress. Here, we show that these essential functions are linked through the Nrf2 transcription factor. To test the hypothesis that activation of Nrf2 provides skin protection under stress conditions, we determined the consequences of pharmacological or genetic activation of Nrf2 in keratinocytes. Surprisingly, mice with enhanced Nrf2 activity in keratinocytes developed epidermal thickening, hyperkeratosis and inflammation resembling lamellar ichthyosis. This resulted from upregulation of the cornified envelope proteins small proline-rich proteins (Sprr) 2d and 2h and of secretory leukocyte peptidase inhibitor (Slpi), which we identified as novel Nrf2 targets in keratinocytes. Since Sprrs are potent scavengers of reactive oxygen species and since Slpi has antimicrobial activities, their upregulation contributes to Nrf2's protective function. However, it also caused corneocyte fragility and impaired desquamation, followed by alterations in the epidermal lipid barrier, inflammation and overexpression of mitogens that induced keratinocyte hyperproliferation. These results identify an unexpected role of Nrf2 in epidermal barrier function, which needs to be considered for pharmacological use of Nrf2 activators.
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/05/2012 18:13
Dernière modification de la notice
08/05/2019 21:09
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