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Elucidation of the molecular mechanism of preferential suppression of fibroblast activity and its application to the treatment of pulmonary fibrosis

Research Project

Project/Area Number 18K06691
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47040:Pharmacology-related
Research InstitutionMusashino University

Principal Investigator

Tanaka Ken-ichiro  武蔵野大学, 薬学部, 講師 (30555777)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords肺線維症 / 線維芽細胞 / 線維化 / 既存薬 / IPF / 呼吸器 / 肺線維芽細胞 / スクリーニング / 細胞死 / ライブラリー / ドラッグリポジショニング
Outline of Final Research Achievements

The onset and exacerbation of idiopathic pulmonary fibrosis (IPF), an intractable disease, involves abnormal proliferation and activation of lung fibroblasts (e.g., collagen overproduction) triggered by alveolar epithelial cell injury caused by reactive oxygen species (ROS). In this study, we aimed to apply compounds (approved drug) that preferentially induce cell death in fibroblasts without damaging alveolar epithelial cells as a therapeutic agent for IPF. As a result, we found that the candidate compound showed efficacy against a mouse model of pulmonary fibrosis. We also found that the efficacy was superior to that of existing drugs such as pirfenidone, and that the candidate compound did not induce side effects in the gastrointestinal tract or liver.

Academic Significance and Societal Importance of the Research Achievements

ピルフェニドンやニンテダニブなどの治療薬は存在するが、有効性を示さない患者が存在することや副作用を誘発することなどから、IPFに対する新規治療薬の開発が望まれている。本研究で用いた候補化合物は、肺線維症に対して既存治療薬より優れた有効性を発揮し、副作用を起こしにくいことを動物モデルを用いて明らかにした。このように本研究では、難病であるIPF対して安全で有効な候補化合物を発見しており、臨床的な意義が大きいと考えている。また、本研究では、候補化合物が線維芽細胞選択的に作用するターゲット候補を発見しているので、今後のIPF治療薬開発における一助となるのではないかと考えている。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (5 results)

All 2021 2020 2019

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Thioredoxin-albumin fusion protein prevents urban aerosol-induced lung injury via suppressing oxidative stress-related neutrophil extracellular trap formation.2021

    • Author(s)
      Tanaka KI, Kubota M, Shimoda M, Hayase T, Miyaguchi M, Kobayashi N, Ikeda M, Ishima Y, Kawahara M.
    • Journal Title

      Environ Pollut.

      Volume: 268(Pt A) Pages: 115787-115787

    • DOI

      10.1016/j.envpol.2020.115787

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Carnosine and Lung Disease2020

    • Author(s)
      Tanaka KI, Kawahara M.
    • Journal Title

      Curr Med Chem

      Volume: 27 Issue: 11 Pages: 1714-1725

    • DOI

      10.2174/0929867326666190712140545

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Idebenone has preventative and therapeutic effects on pulmonary fibrosis via preferential suppression of fibroblast activity2019

    • Author(s)
      Tanaka Ken-ichiro、Shimoda Mikako、Takafuji Ayaka、Hino Yuuki、Sugizaki Toshifumi、Kawahara Masahiro
    • Journal Title

      Proceedings for Annual Meeting of The Japanese Pharmacological Society

      Volume: 92 Issue: 0 Pages: 3-P-084

    • DOI

      10.1254/jpssuppl.92.0_3-P-084

    • NAID

      130007813267

    • ISSN
      2435-4953
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 線維芽細胞選択的に作用する薬の探索と特発性肺線維症治療薬への応用2019

    • Author(s)
      田中 健一郎、下田 実可子、高藤 綾香、日野 優生、杉崎 俊文、川原 正博
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Therapeutic effect of idebenone on pulmonary fibrosis via preferential suppression of fibroblast activity2019

    • Author(s)
      Ken-ichiro Tanaka, Mikako Shimoda, Ayaka Takafuji, Yuki hino, Toshifumi Sugizaki, and Masahiro Kawahara
    • Organizer
      CHEST Congress 2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2022-01-27  

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