A novel Nrf2-miR-29-desmocollin-2 axis regulates desmosome function in keratinocytes.

Details

Serval ID
serval:BIB_BBEF5630AB3C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A novel Nrf2-miR-29-desmocollin-2 axis regulates desmosome function in keratinocytes.
Journal
Nature Communications
Author(s)
Kurinna S., Schäfer M., Ostano P., Karouzakis E., Chiorino G., Bloch W., Bachmann A., Gay S., Garrod D., Lefort K., Dotto G.P., Beer H.D., Werner S.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
2014
Volume
5
Pages
5099
Language
english
Abstract
The Nrf2 transcription factor controls the expression of genes involved in the antioxidant defense system. Here, we identified Nrf2 as a novel regulator of desmosomes in the epidermis through the regulation of microRNAs. On Nrf2 activation, expression of miR-29a and miR-29b increases in cultured human keratinocytes and in mouse epidermis. Chromatin immunoprecipitation identified the Mir29ab1 and Mir29b2c genes as direct Nrf2 targets in keratinocytes. While binding of Nrf2 to the Mir29ab1 gene activates expression of miR-29a and -b, the Mir29b2c gene is silenced by DNA methylation. We identified desmocollin-2 (Dsc2) as a major target of Nrf2-induced miR-29s. This is functionally important, since Nrf2 activation in keratinocytes of transgenic mice causes structural alterations of epidermal desmosomes. Furthermore, the overexpression of miR-29a/b or knockdown of Dsc2 impairs the formation of hyper-adhesive desmosomes in keratinocytes, whereas Dsc2 overexpression has the opposite effect. These results demonstrate that a novel Nrf2-miR-29-Dsc2 axis controls desmosome function and cutaneous homeostasis.
Pubmed
Web of science
Open Access
Yes
Create date
27/11/2014 11:31
Last modification date
20/08/2019 16:29
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