| Project/Area Number |
18K08025
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | Yamagata University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | midkine / nucleolin / 心不全 / 心腎連関 / 低酸素 / 腎臓病 / 心肥大 |
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| Outline of Final Research Achievements |
Chronic kidney disease and chronic pulmonary disease are risk factors for heart failure. Organ hypoperfusion and hypoxia produce midkine (MK) in the lungs and kidneys, and circulating MK is responsible for the exacerbation of heart failure. On the other hand, MK reportedly has a role as a cardioprotective agent. In this study, we focus on Nucleolin, a nuclear protein that binds to MK, to elucidate two mechanisms: 1) how MK increases epidermal growth factor receptor (EGFR) activity and activates cardiac hypertrophy via surface Nucleolin, and 2) the anti-apoptotic effect of Nucleolin, which binds to MK and enters the nucleus. We analyze hearts after transverse aortic stenosis using heart-specific MK overexpressing mice and GAR domain-deficient Nucleolin heart-specific overexpressing mice to clarify the role of MK on cardiac function.
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| Academic Significance and Societal Importance of the Research Achievements |
我々は、Midkine (MK)がEGFRを活性化し左室リモデリングの進展を促すことを報告したが、詳細な機序は不明であった。加えて、MKとNucleolinとの結合によって、EGFR活性が亢進することや左室リモデリングが進展することを明らかにした報告は皆無である。また、NucleolinがMKと結合後に核内に移行するが、核内Nucleolinによる抗アポトーシス効果やMKとの関連性に関しては、報告がない。本研究ではMKとNucleolin複合体が心筋細胞障害、心筋細胞保護のdual effectを発揮する機序に関して理解が深まるため、心不全の新規の治療法の開発につながる重要な基盤研究となる。
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