title: Transcription Factor MafB Coordinates Epidermal Keratinocyte Differentiation.
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.
authors.affiliation: Laboratory of Molecular and Developmental Biology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Miyai
authors.affiliation: Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Michito
authors.initials: M
authors.lastname: Hamada
authors.affiliation: Department of Medical Biochemistry, Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Moriguchi
authors.affiliation: Department of Dermatology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Hiruma
authors.affiliation: Laboratory of Molecular and Developmental Biology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Japan.
authors.forename: Akiyo
authors.initials: A
authors.lastname: Kamitani-Kawamoto
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, Osaka, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Pharmacology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Hara-Chikuma
authors.affiliation: Department of Dermatology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Kenzo
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: 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.
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Kataoka
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D003876:Dermatitis, Atopic / Q000235:genetics / Q000503:physiopathology; D015536:Down-Regulation; D000078404:Epidermal Cells; D000091344:Filaggrin Proteins; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D015151:Immunoblotting; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology; D000090062:Kruppel-Like Factor 4; D051258:MafB Transcription Factor / Q000235:genetics*; D051379:Mice; D046228:Microarray Analysis; D038081:Organogenesis / Q000235:genetics; D011565:Psoriasis / Q000235:genetics / Q000503:physiopathology; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; C490407:MAFB protein, human; D051258:MafB Transcription Factor; D014157:Transcription Factors