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Elucidation of the molecular mechanisms underlying persistent pruritus in primary biliary cholangitis

Research Project

Project/Area Number 18K06707
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47040:Pharmacology-related
Research InstitutionNiigata University of Pharmacy and Medical and Life Sciences

Principal Investigator

Maeda Takehiko  新潟薬科大学, 薬学部, 教授 (50271010)

Co-Investigator(Kenkyū-buntansha) 長谷川 拓也  新潟薬科大学, 薬学部, 助手 (80813287)
川原 浩一  新潟薬科大学, 薬学部, 教授 (10347015)
Project Period (FY) 2018-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsそう痒 / 胆汁うっ滞性そう痒 / 表皮 / グルココルチコイド / 胆汁うっ滞 / TRPチャネル / ガストリン放出ペプチド / DREADD / 脊髄 / グリア細胞
Outline of Final Research Achievements

We made a mouse model of cholestatic pruritus (CP) to investigate the underlying molecular mechanisms. Bile duct ligation (BDL) was performed to establish a mouse model of CP. BDL led to increased serum levels of total bile acid, liver damage and spontaneous hind paw scratching in mice. Given the altered expression of gastrin-releasing peptide (GRP) in the skin and dorsal root ganglia (DRG) of the model mice, the study focused on functionally relevant TRP channels. In the DRG, TRPV4 expression increased, while in the skin, it decreased. CP model and TRPV4 knockout mice both revealed impaired skin moisture retention. These results suggest that skin TRPV4 may play a role in physiological skin barrier function and cholestatic pruritus.

Academic Significance and Societal Importance of the Research Achievements

慢性肝疾患では胆汁の流出が停滞する胆汁うっ滞の症状が認められ、全身性かつ慢性のかゆみを伴うことがある。かゆみは生活動作や睡眠の障害を招き、QOLを著しく阻害するが、アレルギー性疾患と比較して、薬物療法は限られている。本研究成果は、難治性遷延性のそう痒症の発現機序解明に向けた基礎的資料となり得るものであり、慢性そう痒を伴う疾患の治療標的検索にも貢献するものである。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (7 results)

All 2024 2022 2021 2020 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (5 results) Remarks (1 results)

  • [Journal Article] Truncated <scp>GPNMB</scp>, a microglial transmembrane protein, serves as a scavenger receptor for oligomeric β‐amyloid peptide<sub>1‐42</sub> in primary type 1 microglia2024

    • Author(s)
      Kawahara Kohichi、Hasegawa Takuya、Hasegawa Noa、Izumi Taisei、Sato Koji、Sakamaki Toshiyuki、Ando Masayuki、Maeda Takehiko
    • Journal Title

      Journal of Neurochemistry

      Volume: in press Issue: 7 Pages: 1317-1339

    • DOI

      10.1111/jnc.16078

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 胆汁うっ滞性掻痒モデルのそう痒行動におけるTRPチャネルの機能的関与2022

    • Author(s)
      長谷川 拓也,斎須 拓哉,藤原 関斗,川原 浩一,前田 武彦
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] 9月齢5xFADマウスの記憶障害に及ぼすGpnmb遺伝子の影響2021

    • Author(s)
      前田武彦
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] 新規癌悪液質マウスモデルの確立と特性2020

    • Author(s)
      前田武彦
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] アルツハイマー病モデルマウスにおけるGpnmb遺伝子の機能解析2020

    • Author(s)
      川原 浩一、熊倉 夏希、小嶋 雪菜、長谷川 拓也、前田 武彦
    • Organizer
      第93回日本薬理学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 肺がん骨移植による悪液質モデルの作製と解析2020

    • Author(s)
      長谷川 拓也、山崎 知槻、羽田 裕介、川原 浩一、前田 武彦
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Research-status Report
  • [Remarks] 新潟薬科大学薬学部薬効薬理学研究室

    • URL

      https://nupalspharmacology.wixsite.com/-lab

    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2025-01-30  

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