Fatty acid metabolism and cardiomyocyte cell cycle regulation

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22629
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• 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): 2019-06-28 – 2021-03-31
• Keywords: 心筋細胞 / 細胞周期 / ミトコンドリア / 脂肪酸β酸化 / 心筋梗塞

Outline of Final Research Achievements

The adult mammalian heart is incapable of regeneration following myocardial injury mainly due to the lack of proliferative capacity in vast majority of cardiomyocytes. In contrast, early neonatal mammals can regenerate lost myocardium through proliferation of pre-existing cardiomyocytes. However, cardiomyocyte cell cycle is arrested in short period of time after birth.
In this study we assessed the role of fatty acid metabolism in cardiomyocyte cell cycle regulation in the neonatal heart. We identified a new regulator, namely AMPK, which is inactivated in neonatal cardiomyocytes and is responsible for the regulation of cardiomyocyte cell cycle. We are currently testing whether artificial regulation of AMPK can induce cardiac regeneration in postnatal mice.

Free Research Field

再生生物学

Academic Significance and Societal Importance of the Research Achievements

我々を含む脊椎動物では，心筋細胞が細胞周期に入る能力と心臓再生能とは完全に対応しており，心筋細胞の細胞周期制御機構の理解は，新たな心臓再生法の開発のためには不可欠である．我々は出生後の心筋細胞において細胞周期制御を担う新規因子AMPKを同定した．本因子AMPKの操作により心筋細胞増殖による心筋再生が誘導可能であれば，心疾患に対する新規治療法の開発につながる可能性があると考えられる．