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Nrf2 links epidermal barrier function with antioxidant defense

Nrf2 links epidermal barrier function with antioxidant defense

https://devfeature-collection.sl.nsw.gov.au/record/TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3403295

Nrf2 links epidermal barrier function with antioxidant defense

About this item

Full title

Nrf2 links epidermal barrier function with antioxidant defense

Publisher

London: Nature Publishing Group UK

Journal title

EMBO molecular medicine, 2012-05, Vol.4 (5), p.364-379

Language

English

Formats

Publication information

Publisher

London: Nature Publishing Group UK

More information

Scope and Contents

Contents

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.
→See accompanying article
http://dx.doi.org/10.1002/emmm.201200223...

Alternative Titles

Full title

Nrf2 links epidermal barrier function with antioxidant defense

Identifiers

Primary Identifiers

Record Identifier

TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3403295

Permalink

https://devfeature-collection.sl.nsw.gov.au/record/TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3403295

Other Identifiers

ISSN

1757-4676

E-ISSN

1757-4684

DOI

10.1002/emmm.201200219

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