Molecular mechanisms of the development of intractable dermatitis caused by abnormal enzymatic activity of calpain

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07044
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: HATA Shoji 公益財団法人東京都医学総合研究所, 基礎医科学研究分野, 主席研究員 (10392375)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: カルパイン / 乾癬

Outline of Final Research Achievements

The epidermis, located at the outermost layer of the skin, is largely composed of keratinocytes, and serves as a biological barrier. Psoriasis is a intractable inflammatory disease characterized by hyperproliferation of keratinocytes. However, the underlying mechanisms remain poorly understood. This research revealed the involvement of CAPN12, a member of intracellular Ca2+-dependent protease (calpain) family, in the development of psoriasis. Further analysis suggested that CAPN12 regulates the differentiation of keratinolytes, and that upregulation of CAPN12 contributes to the development of psoriasis.

Free Research Field

細胞内タンパク質分解

Academic Significance and Societal Importance of the Research Achievements

乾癬は難治性の皮膚炎で、発症のメカニズムは十分に解明されていない。本研究では、乾癬の発症に、細胞内カルシウム依存性プロテアーゼであるカルパイン12(CAPN12)が関与することを見出し、マウスでCAPN12の働きを抑えると症状を抑制できることを示した。CAPN12がどのように乾癬発症に作用するのかを今後明確にすることで、CAPN12を標的とした新規治療法開発に繋がる可能性がある。