Transcription Factor MafB Coordinates Epidermal Keratinocyte Differentiation

Masashi Miyai, Michito Hamada, Takashi Moriguchi, Junichiro Hiruma, Akiyo Kamitani-Kawamoto, Hajime Watanabe, Mariko Hara-Chikuma, Kenzo Takahashi, Satoru Takahashi, Kohsuke Kataoka

研究成果: Article査読

18 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1848-1857
ページ数10
ジャーナルJournal of Investigative Dermatology
136
9
DOI
出版ステータスPublished - 2016 9 1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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