Role of temperature-sensitive TRP channels in skin inflammatory diseases and their therapeutic application

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08340
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Gunma University
• Principal Investigator: Motegi Sei-ichiro 群馬大学, 大学院医学系研究科, 教授 (20420185)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 尋常性乾癬 / TRPV4 / 温度感受性TRPチャネル

Outline of Final Research Achievements

Using a mouse model of psoriasis vulgaris, a cutaneous inflammatory disease, we investigated the role of TRPV4, a temperature-sensitive channel, in the pathogenesis and its regulatory mechanism. We found that TRPV4 expression is upregulated in the lesional skin of psoriasis vulgaris patients, and that TRPV4 gene-deficient mice show improved psoriasis-like skin eruption compared to wild-type mice. The study also revealed that TRPV4 plays a role in the pathogenesis of psoriasis-like skin lesions, and that TRPV4 antagonist treatment improves the skin lesions, suggesting the possibility of future therapeutic development.

Free Research Field

皮膚疾患　免疫疾患

Academic Significance and Societal Importance of the Research Achievements

皮膚（表皮細胞、神経、線維芽細胞）に発現するTRPV4が皮膚バリア機能だけではなく、痒みといった皮膚感覚の制御と免疫細胞の制御を介して、皮膚炎症性疾患である尋常性乾癬の病態に寄与することを明らかにした。表皮細胞や免疫細胞、神経におけるTRPV4を介した乾癬の病態制御という独自性の高い切り口から、発生機序や病態を解明した。また、TRPV4アンタゴニストの投与によって皮疹が改善することも見出し、この成果が新たな治療法の開発に貢献できることが期待される。