Investigation of the cardiomyocyte-specific DNA damage response

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H03662
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Toho University
• Principal Investigator: NAITO Atsuhiko 東邦大学, 医学部, 教授 (10588891)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 心筋細胞 / DNA損傷応答 / SWI/SNF複合体

Outline of Final Research Achievements

We hypothesized that cardiomyocyte-specific DNA damage response play a role in cell cycle exit of cardiomyocyte after birth. To test this hypothesis, we tried to develop a system that could reproducibly and controllably induce DNA damage in myocardial cells and non-myocardial cells using genetic engineering techniques. However, we were unable to develop a system with sufficient reproducibility.
On the other hand, through the observations made during the course of the initial research plan, we discovered that the SWI/SNF complex controls the division and proliferation of myocardial cells to the opposite direction in an ATPase subunit-specific manner. We are convinced that this chromatin remodeling complex ATPase subunit-specific regulation of DNA damage response and gene regulation is involved in the mechanism by which cardiomyocytes exit the cell cycle after birth.

Free Research Field

細胞生理学

Academic Significance and Societal Importance of the Research Achievements

心筋細胞が生後に分裂増殖を停止する仕組みを明らかにすることで、心筋細胞を細胞周期に復帰させて分裂増殖を誘導する新たな再生医療の開発につながる可能性がある。また、がん細胞に対して心筋細胞が細胞周期を離脱する仕組みを導入する技術を開発できればがんに対する新たな治療法となる可能性がある。さらに、心筋細胞がROSによる持続的なDNA損傷に対して細胞死や細胞老化を引き起こすことなく機能を保ち続ける仕組みを明らかにすることで老化に関連する疾患の治療法開発につながる可能性がある。