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A novel Nrf2-miR-29-desmocollin-2 axis regulates desmosome function in keratinocytes.
- Source :
-
Nature communications [Nat Commun] 2014 Oct 06; Vol. 5, pp. 5099. Date of Electronic Publication: 2014 Oct 06. - Publication Year :
- 2014
-
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.
- Subjects :
- Animals
Base Sequence
Cell Line, Tumor
Chromatin Immunoprecipitation
CpG Islands
DNA Methylation
Gene Expression Regulation
Gene Silencing
Homeostasis
Humans
Membrane Glycoproteins metabolism
Mice
Mice, Transgenic
Molecular Sequence Data
Skin metabolism
Desmocollins metabolism
Desmosomes metabolism
Keratinocytes cytology
MicroRNAs metabolism
NF-E2-Related Factor 2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 5
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 25283360
- Full Text :
- https://doi.org/10.1038/ncomms6099