マツイ　タケシ   Takeshi Matsui   松井　毅    所属   応用生物学部 応用生物学科    職種   教授
言語種別	英語
発行・発表の年月	2019/09
形態種別	学術論文
査読	査読あり
標題	Filaggrin expression and processing deficiencies impair corneocyte surface texture and stiffness in mice
執筆形態	共著
掲載誌名	Journal of Investigative Dermatology
掲載区分	国外
出版社・発行元	ELSEVIER
巻・号・頁	140(3),pp.615-623
総ページ数	9
国際共著	国際共著
著者・共著者	Jacob P Thyssen, Ivone Jakasa, Christoph Riethmüller, Michael P Schön, Andrea Braun, Marek Haftek, Padraic G Fallon, Jacek Wróblewski, Hieronim Jakubowski, Leopold Eckhart, Wim Declercq, Sjors Koppes, Kristiane A Engebretsen, Charlotte Bonefeld, Alan D Irvine, Sokhna Keita-Alassane, Michel Simon, Hiroshi Kawasaki, Akiharu Kubo, Masayuki Amagai, Takeshi Matsui, Sanja Kezic
概要	Abundant corneocyte surface protrusions, observed in patients with atopic dermatitis with filaggrin loss-of-function mutations, are inversely associated with levels of natural moisturizing factors (NMFs) in the stratum corneum. To dissect the etiological role of NMFs and filaggrin deficiency in surface texture alterations, we examined mouse models with genetic deficiencies in the synthesis or degradation of filaggrin monomers for NMFs, cell stiffness (elastic modulus) and corneocyte surface protrusion density (dermal texture index). Five neonatal and adult mouse models carrying inactivating mutations of SASPase (Sasp-/-), filaggrin (Flgft/ft and Flg-/-), filaggrin-hornerin (FlgHrnr-/-), and bleomycin hydrolase (Blmh-/-) were investigated. Sasp-/- and Flg-/- were on the hairless mouse background. Atomic force microscopy was used to determine elastic modulus and dermal texture index. Corneocytes of each neonatal as well as hairless adult knockout mouse exhibited an increased number of protrusions and decreased elastic modulus. In these mice, NMFs were reduced except for Sasp-/-. Dermal texture index was inversely correlated with NMFs and elastic modulus. Our findings demonstrate that any filaggrin-NMF axis deficiency can affect corneocyte mechanical properties in mice and likely in humans. Differences in NMFs and corneocyte surface texture between neonatal and adult as well as hairless and hairy mice emphasize the need for carefully selecting the most appropriate animal models for studies.