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

Research Project

Project/Area Number 21K08340
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53050:Dermatology-related
Research InstitutionGunma 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
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords尋常性乾癬 / TRPV4 / 温度感受性TRPチャネル / 温度感受性チャネル / アトピー性皮膚炎
Outline of Research at the Start

温度感受性チャネルは、温度だけではなく様々な化学的・物理的刺激を感受するセンサーとして生体機能に関わっている。今回我々は、皮膚炎症性疾患である尋常性乾癬とアトピー性皮膚炎の病態における温度感受性チャネルの役割を解明する。温度感受性チャネルの病態における役割と制御機構について解明し、治療への応用を目指すことを目的とする。

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.

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。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (2 results)

All 2023 2022

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] TRPV4 Regulates the Development of Psoriasis by Controlling Adenosine Triphosphate Expression in Keratinocytes and the Neuroimmune System2023

    • Author(s)
      Amalia Syahla Nisaa、Baral Hritu、Fujiwara Chisako、Uchiyama Akihiko、Inoue Yuta、Yamazaki Sahori、Ishikawa Mai、Kosaka Keiji、Sekiguchi Akiko、Yokoyama Yoko、Ogino Sachiko、Torii Ryoko、Hosoi Mari、Shibasaki Koji、Motegi Sei-ichiro
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 143 Issue: 12 Pages: 2356-2365

    • DOI

      10.1016/j.jid.2023.05.009

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] TRPV4 regulates psoriasis-like dermatitis via enhancement of Th17 pathway by ATP and neuropeptides production in mouse model2022

    • Author(s)
      Syahla N. Amalia, Akihiko Uchiyama, Hritu Baral, Chisako Fujiwara, Yuta Inoue, Yoko Yokoyama, Sachiko Ogino, Ryoko Torii, Mari Hosoi, Sei-ichiro Motegi
    • Organizer
      The 47th Annual Meeting of the Japanese Society for Investigative Dermatology
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research

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Published: 2021-04-28   Modified: 2025-01-30  

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