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Hypoxia Signaling and Cardiac Regeneration

Research Project

Project/Area Number 17H05083
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Cardiovascular medicine
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Wataru Kimura  国立研究開発法人理化学研究所, 生命機能科学研究センター, チームリーダー (60452182)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥25,610,000 (Direct Cost: ¥19,700,000、Indirect Cost: ¥5,910,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Keywords心筋細胞 / 細胞周期 / 低酸素シグナル / ミトコンドリア / 酸化ストレス / 心筋梗塞 / 心不全 / 酸素代謝 / 心筋再生 / 心臓学 / 循環器 / 再生医療
Outline of Final Research Achievements

The aim of this research is to characterize the role of hypoxia signaling in cardiomyocyte cell cycle regulation. Firstly, we found that mitochondrial metabolism plays critical roles in cardiomyocyte cell cycle arrest in the postnatal heart. Secondly, in order to determine the roles of hypoxia signaling in proliferative cardiomyocytes in the adult heart, we utilized conditional knock-in and knock-out mouse model and found that hypoxia inducible factor 1 alpha (hif1a) and amelioration of oxidative stress are both critical for maintenance of cardiomyocyte turnover in the adult heart. Our research provides a unique insight into mechanisms underlying cardiomyocyte cell cycle, and may pave the way to induce cardiomyocyte proliferation in the human infarcted heart.

Academic Significance and Societal Importance of the Research Achievements

本研究により,心筋細胞の細胞周期制御を担う新たな因子としてミトコンドリア代謝と低酸素シグナルが同定された.この成果は代謝と細胞周期とをつなぐシグナル伝達経路の一端を明らかにしたことに加えて,心筋細胞増殖を介した心筋再生達成のための基礎となる知見を提供するものである.

Report

(2 results)
  • 2019 Final Research Report ( PDF )
  • 2018 Annual Research Report
  • Research Products

    (12 results)

All 2019 2018

All Journal Article (2 results) Presentation (9 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results) Book (1 results)

  • [Journal Article] Oxidative Metabolism Regulates Cardiomyocyte Cell Cycle and Cardiac Regeneration2018

    • Author(s)
      木村航
    • Journal Title

      生化学

      Volume: 90 Issue: 3 Pages: 385-387

    • DOI

      10.14952/SEIKAGAKU.2018.900385

    • NAID

      40021622626

    • ISSN
      0037-1017
    • Year and Date
      2018-06-25
    • Related Report
      2018 Annual Research Report
  • [Journal Article] 心筋細胞増殖制御機構の解明2018

    • Author(s)
      坂口あかね、木村航
    • Journal Title

      心臓

      Volume: 50 Pages: 1276-1282

    • NAID

      130007786250

    • Related Report
      2018 Annual Research Report
  • [Presentation] 環境応答と心臓再生能2019

    • Author(s)
      木村 航
    • Organizer
      新潟分子心血管セミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 酸化ストレス応答と心筋恒常性維持機構2019

    • Author(s)
      木村 航
    • Organizer
      公開シンポジウム「生物は加齢とともにどのように変化するのか:最先端研究から見えてきたもの」
    • Related Report
      2018 Annual Research Report
  • [Presentation] Hypoxia and Cardiac Regeneration2018

    • Author(s)
      木村 航
    • Organizer
      Weinstein 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Hypoxia-Induced Cardiomyocyte Proliferation and Cardiac Regeneration2018

    • Author(s)
      木村 航
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Myocardial Regeneration by Engineering Mitochondrial Turnover2018

    • Author(s)
      木村 航
    • Organizer
      第2回日本循環器学会基礎研究フォーラム
    • Related Report
      2018 Annual Research Report
  • [Presentation] DNA 損傷応答と心臓再生2018

    • Author(s)
      木村 航
    • Organizer
      日本放射線影響学会第61回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 酸化的代謝と心筋再生2018

    • Author(s)
      木村 航
    • Organizer
      第9回山口県循環器病セミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] DNA損傷応答による心筋細胞周期制御と心臓再生能2018

    • Author(s)
      木村 航
    • Organizer
      千里ライフサイエンスセミナーM1 老化メカニズムと疾患制御
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 酸化ストレス応答と心筋再生2018

    • Author(s)
      木村 航
    • Organizer
      大阪大学循環器内科セミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Book] 再生医療の開発戦略と最新研究事例集2019

    • Author(s)
      木村 航 他
    • Total Pages
      420
    • Publisher
      技術情報協会
    • ISBN
      9784861047374
    • Related Report
      2018 Annual Research Report

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Published: 2017-04-28   Modified: 2025-01-30  

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