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Elucidation of aging lung pathophysiology through sphingolipid signaling

Research Project

Project/Area Number 19K07864
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52010:General internal medicine-related
Research InstitutionKanazawa University

Principal Investigator

ISHIMARU KAZUHIRO  金沢大学, 医学系, 協力研究員 (70595446)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords肺線維症 / スフィンゴ脂質代謝 / 老年医学 / 間質性肺炎
Outline of Research at the Start

年齢と共に、肺の機能は少しずつ低下し息切れなどの原因となります。その中でも間質性肺炎・肺線維症という病態は指定難病であり、これに陥ると肺の機能は急激に悪くなり機能を回復あるいは維持する事が難しいと言われています。しかし、病院で使用できる特効薬は殆ど無く、新しい薬の開発が必要だと考えられています。
新しい薬の鍵は、「間質性肺炎・肺線維症という病気がなぜ起こるのか?」という疑問を探ると見えてきます。今回私達は「スフィンゴ脂質代謝」という体のしくみが、この病気を良くしたり悪くしたりする原因の一つである可能性を、動物実験で確認しました。この研究はそのしくみをより詳細に調べるための研究です。

Outline of Final Research Achievements

There is an intractable disease called interstitial pneumonia / pulmonary fibrosis, which is different from the decline in lung function due to aging, and there are almost no silver bullets, and it is thought that new drug development is necessary. The key to new drug development is to elucidate the pathophysiology of "why interstitial pneumonia / pulmonary fibrosis occur?". Indeed, many cases with unknown cause have been reported. This time, we discovered that the S1P2 receptor may be involved in the pathophysiology of pulmonary fibrosis in the biological system called "sphingolipid metabolism". But complex interactions between pulmonary constituent cells were suggested in the pathogenesis of lung fibrosis via S1P2 receptor.

Academic Significance and Societal Importance of the Research Achievements

本研究成果はスフィンゴ脂質代謝、特に生理活性因子S1Pとその受容体サブタイプという斬新な観点から見いだされた、原因不明(特発性)あるいは薬剤により誘導される肺線維症・間質性肺炎の病態機序解明の糸口と考えられ、肺機能を健全に保ち長寿社会を支える可能性を秘めた画期的な治療薬開発に繋がる重要な情報基盤となる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (2 results)

All 2020 2019

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

  • [Journal Article] Class II phosphatidylinositol 3-kinase α and β isoforms are required for vascular smooth muscle Rho activation, contraction and blood pressure regulation in mice2020

    • Author(s)
      Islam Shahidul、Yoshioka Kazuaki、Aki Sho、Ishimaru Kazuhiro、Yamada Hiroki、Takuwa Noriko、Takuwa Yoh
    • Journal Title

      The Journal of Physiological Sciences

      Volume: 70 Issue: 1 Pages: 18-18

    • DOI

      10.1186/s12576-020-00745-2

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sphingosine kinase-2 prevents macrophage cholesterol accumulation and atherosclerosis by stimulating autophagic lipid degradation2019

    • Author(s)
      Ishimaru Kazuhiro、Yoshioka Kazuaki、Kano Kuniyuki、Kurano Makoto、Saigusa Daisuke、Aoki Junken、Yatomi Yutaka、Takuwa Noriko、Okamoto Yasuo、Proia Richard L.、Takuwa Yoh
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 18329-18329

    • DOI

      10.1038/s41598-019-54877-6

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

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Published: 2019-04-18   Modified: 2023-01-30  

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