Elucidation of molecular mechanism of skin barrier formation by acylceramide.

2018 Fiscal Year Final Research Report

• Project/Area Number: 15H05589
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Functional biochemistry
• Research Institution: Hokkaido University
• Principal Investigator: Ohno Yusuke 北海道大学, 薬学研究院, 助教 (50611498)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: アシルセラミド / セラミド / スフィンゴ脂質 / 脂肪酸 / 魚鱗癬 / アトピー性皮膚炎

Outline of Final Research Achievements

Although acylceramide is an essential lipid for skin barrier formation, the pathway of acylceramide synthesis has not been elucidated. Impairment of acylceramide production causes a skin disorder ichthyosis, and several ichthyosis causative genes have been identified. Among them, there exists many genes with unknown function. and the molecular mechanism of the pathogenesis caused by gene mutation remain poorly understood. In this research project, we elucidated the acylceramide synthetic pathway and demonstrated that CYP4F22, ACSVL4 and PNPLA1, enzymes with unknown functions, are involved in the acylceramide synthesis. Furthermore, we revealed that NIPAL4 gene mutations result in aberrant gene expressions including acylceramide synthesis-related enzymes due to decreased Mg2+ uptake, leading to pathogenesis of ichthyosis.

Free Research Field

脂質生化学

Academic Significance and Societal Importance of the Research Achievements

アシルセラミド量の減少は皮膚バリア機能の低下を引き起こす。皮膚バリアの低下によりアレルゲンや病原体の侵入が容易になるため，アシルセラミド量の減少は魚鱗癬のみならずアトピー性皮膚炎の増悪や感染症のリスク上昇につながる。本研究は皮膚バリア脂質であるアシルセラミドの産生経路を世界で初めて明らかにし，この成果は皮膚バリア機能低下に起因する様々な疾患の治療薬，治療法の開発の重要な糸口となると考えられる。