Elucidation of the mechanisms underlying maintenance and disruption of T-tubule membrane in cardiomyocytes for the creation of novel therapeutic strategies for heart failure
| Project/Area Number |
17H04740
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biomedical engineering/Biomaterial science and engineering
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| Research Institution | Nagoya Institute of Technology (2018-2020)
Kawasaki Medical School (2017) |
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Principal Investigator |
Ujihara Yoshihiro 名古屋工業大学, 工学(系)研究科(研究院), 准教授 (80610021)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥25,870,000 (Direct Cost: ¥19,900,000、Indirect Cost: ¥5,970,000)
Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2019: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000)
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| 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 / バイオメカニクス / 脂質 / 流動性 / メカノフィジオロジー / ホメオスタシス |
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| 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.
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| 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．
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Report
(5 results)
Research Products
(35 results)
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[Journal Article] Loss of Endogenous HMGB2 Promotes Cardiac Dysfunction and Pressure Overload-Induced Heart Failure in Mice2019
Author(s)
Sato M, Miyata K, Tian Z, Kadomatsu T, Ujihara Y, Morinaga J, Horiguchi H, Endo M, Zhao J, Zhu S, Sugizaki T, Igata K, Muramatsu M, Minami T, Ito T, Bianchi ME, Mohri S, Araki K, Node K, Oike Y
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Journal Title
Circulation Journal
Volume: 83
Issue: 2
Pages: 368-378
DOI
NAID
ISSN
1346-9843, 1347-4820
Year and Date
2019-01-25
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] 伸びることを拒んできた私達哺乳類の心臓：心室拡張機能の進化的考察2017
Author(s)
本田 威, 田村 太志, 花島 章, 氏原 嘉洋, 山澤 隆彦, 古川 博史, 橋本 謙, 渡部 芳子, 柚木 靖弘, 田淵 篤, 種本 和雄, 毛利 聡
Organizer
第110回日本循環器学会中国・四国合同地方会
Related Report
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