Elucidating the significance of mitophagy in cardiomyocyte dedifferentiation for cardiac regeneration therapy

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22707
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0801:Pharmaceutical sciences and related fields
• Research Institution: Osaka University
• Principal Investigator: Tanaka Shota 大阪大学, 薬学研究科, 助教 (80880294)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 心筋再生 / マイトファジー

Outline of Final Research Achievements

Cardiac diseases are generally poor prognosis because cardiomyocytes rarely perform cell division and it is difficult to repair damaged heart. Therefore, to cure cardiac diseases completely, it is necessary to elucidate the mechanisms of cardiomyocytes proliferation.
It remains unclear whether mitophagy promotes cardiomyocytes proliferation. PINK1 is a mitophagy promoting factor and the neonatal rat cardiomyocytes (NRCM) which induced PINK1 overexpression more expressed cell cycle markers compared with Luciferase overexpressing NRCM. Moreover, PINK1 overexpressing NRCM increased Igf2 mRNA, as a pro-proliferation factor, and Myh7/Myh6 ratio, as an immature cardiomyocytes indicator. This study suggests that PINK1 promotes cardiomyocytes proliferation through mitophagy activation.

Free Research Field

循環薬理学

Academic Significance and Societal Importance of the Research Achievements

心疾患は一般的に予後不良であるが、これは心筋細胞の増殖能が極めて低く、傷害を受けた心筋組織が回復しないことに起因する。そのため、心疾患の根本的な治療を行うためには心筋細胞の増殖メカニズムの解明が求められる。本研究は、PINK1の過剰発現が心筋細胞の脱分化、ならびに細胞増殖を促進させる可能性を示した。今後、本研究をさらに発展させることにより、心疾患の新たな治療法の開発につながることができると考えている。