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J Invest Dermatol. 2016 Sep;136(9):1848-1857. doi: 10.1016/j.jid.2016.05.088. Epub 2016 May 18.

Transcription Factor MafB Coordinates Epidermal Keratinocyte Differentiation.

Author information

1
Laboratory of Molecular and Developmental Biology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Japan.
2
Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
3
Department of Medical Biochemistry, Graduate School of Medicine, Tohoku University, Sendai, Japan.
4
Department of Dermatology, Tokyo Medical University, Tokyo, Japan.
5
Department of Biotechnology, Graduate School of Engineering, Osaka University, Osaka, Japan.
6
Department of Pharmacology, Keio University School of Medicine, Tokyo, Japan.
7
Department of Dermatology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
8
Laboratory of Molecular and Developmental Biology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Japan; Laboratory of Molecular Medical Bioscience, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan. Electronic address: kkataoka@tsurumi.yokohama-cu.ac.jp.

Abstract

Mammalian epidermis is a stratified epithelium composed of distinct layers of keratinocytes. The outermost cornified layer is a primary barrier that consists of a cornified envelope, an insoluble structure assembled by cross-linked scaffold proteins, and a surrounding mixture of lipids. Skin keratinocytes undergo a multistep differentiation process, but the mechanism underlying this process is not fully understood. We demonstrate that the transcription factor MafB is expressed in differentiating keratinocytes in mice and is transcriptionally upregulated upon human keratinocyte differentiation in vitro. In MafB-deficient mice, epidermal differentiation was partially impaired and the cornified layer was thinner than in wild-type mice. On the basis of transcriptional profiling, we detected reduced expression levels of a subset of cornified envelope genes, for example, filaggrin and repetin, in the MafB(-/-) epidermis. By contrast, the expression levels of lipid metabolism-related genes, such as Alox12e and Smpd3, increased. The upregulated genes in the MafB(-/-) epidermis were enriched for putative target genes of the transcription factors Gata3, Grhl3, and Klf4. Immunohistochemical analysis of skin biopsy samples revealed that the expression levels of filaggrin and MafB were significantly reduced in patients with human atopic dermatitis and psoriasis vulgaris. Our results indicate that MafB is a component of the gene expression program that regulates epidermal keratinocyte differentiation.

PMID:
27208706
DOI:
10.1016/j.jid.2016.05.088
[Indexed for MEDLINE]
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