Elucidation of the mechanisms underlying maintenance and disruption of T-tubule membrane in cardiomyocytes for the creation of novel therapeutic strategies for heart failure

2020 Fiscal Year Final Research Report

• Project/Area Number: 17H04740
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Nagoya Institute of Technology (2018-2020); Kawasaki Medical School (2017)
• Principal Investigator: Ujihara Yoshihiro 名古屋工業大学, 工学(系)研究科(研究院), 准教授 (80610021)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 心筋細胞 / T管膜 / 心不全 / リモデリング / カルシウム / メカニカルストレス

Outline of Final Research Achievements

The T-tubule membrane, a specialized membrane structure of cardiomyocytes, is critical for efficient contraction and relaxation of the cardiomyocytes. Since disruption of the T-tubule membrane structure triggers the onset of heart failure, this study aimed to elucidate the mechanisms underlying the support and disruption of the T-tubule membrane structure by analyzing the progression of heart failure in mice. We found that the abnormal localization of Junctophilin-2, a protein that bridges T-tubules and SR membranes, causes the disruption of the T-tubule membrane. We proposed the possibility that the T-tubule membrane structure can be maintained by controlling the factors that cause Junctophilin-2 mislocalization.

Free Research Field

生体医工学

Academic Significance and Societal Importance of the Research Achievements

高齢化に伴い，心不全患者数が増加しており，その対策は喫緊の課題です．心筋細胞の特殊膜構造であるT管膜の崩壊は，心不全発症の引き金になることが知られていますが，その崩壊のメカニズムは不明でした．本研究では，マウスの心不全進行過程を詳細に解析することで，T管膜の崩壊するメカニズムの一端を解明しました．この成果は，T管膜の崩壊に起因する心不全の早期診断やT管膜構造の維持による新たな心不全治療の開発に貢献すると考えられます．