| Project/Area Number |
18K15873
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
Ito Shin 国立研究開発法人国立循環器病研究センター, 病院, 室長 (20796560)
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| Project Period (FY) |
2018-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 心肥大 / スプライシング / 心不全 / 遺伝子変異 / 遺伝子解析 |
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| Outline of Final Research Achievements |
In this study, we investigated the regulation of Mtus1A expression, a suppressor of cardiac hypertrophy, and found that Mtus1A is expressed specifically in cardiomyocytes and localized in mitochondria. Importin 7 was identified as a binding protein for Mtus1A, suggesting that Mtus1A binds to Importin 7 in mitochondria and inhibits nuclear transport of phosphorylated ERK, thereby suppressing cardiac hypertrophy. Furthermore, we tried to identify the transcription factor of Mtus1 but could not. Genomic analysis of patients with severe heart failure and national and international databases were used to identify genetic mutations in Mtus1, but mutations involved in the pathogenesis of heart failure could not be identified.
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| Academic Significance and Societal Importance of the Research Achievements |
心不全患者の予後は改善してきたが、現在の治療薬やデバイス治療に反応しない予後不良な心不全患者が未だ多く存在する。また、肥大型心筋症などでは、心肥大を抑制する治療法が存在しないのが現状である。本研究では、Mtus１Aの結合タンパクであるImportin 7を同定し、Mtus1Aが心肥大を抑制する機序の解明につながった。本研究の成果は、将来的にMtus1Aを介した心不全・心肥大の新たな治療法の開発につながると考えられる。
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