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	2011/03
形態種別	学術論文
査読	査読あり
標題	SASPase regulates stratum corneum hydration through profilaggrin-to-filaggrin processing
執筆形態	共著
掲載誌名	EMBO Molecular Medicine
掲載区分	国外
出版社・発行元	EMBOpress
巻・号・頁	3(6),pp.320-333
総ページ数	4
担当区分	筆頭著者,責任著者
著者・共著者	Takeshi Matsui, Kenichi Miyamoto, Akiharu Kubo, Hiroshi Kawasaki, Tamotsu Ebihara, Kazuya Hata, Shinya Tanahashi, Shizuko Ichinose, Issei Imoto, Johji Inazawa, Jun Kudoh, Masayuki Amagai
概要	The stratum corneum (SC), the outermost layer of the epidermis, acts as a barrier against the external environment. It is hydrated by endogenous humectants to avoid desiccation. However, the molecular mechanisms of SC hydration remain unclear. We report that skin-specific retroviral-like aspartic protease (SASPase) deficiency in hairless mice resulted in dry skin and a thicker and less hydrated SC with an accumulation of aberrantly processed profilaggrin, a marked decrease of filaggrin, but no alteration in free amino acid composition, compared with control hairless mice. We demonstrated that recombinant SASPase directly cleaved a linker peptide of recombinant profilaggrin. Furthermore, missense mutations were detected in 5 of 196 atopic dermatitis (AD) patients and 2 of 28 normal individuals. Among these, the V243A mutation induced complete absence of protease activity in vitro, while the V187I mutation induced a marked decrease in its activity. These findings indicate that SASPase activity is indispensable for processing profilaggrin and maintaining the texture and hydration of the SC. This provides a novel approach for elucidating the complex pathophysiology of atopic dry skin.
外部リンクURL	https://www.embopress.org/doi/full/10.1002/emmm.201100140