Hypoxia Signaling and Cardiac Regeneration

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H05083
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Cardiovascular medicine
• Research Institution: Institute 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
• 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

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.

Free Research Field

再生生物学

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．