| Project/Area Number |
18H02807
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | Osaka University |
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Principal Investigator |
OTSU Kinya 大阪大学, 医学系研究科, 招へい教授 (20294051)
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| Co-Investigator(Kenkyū-buntansha) |
種池 学 大阪大学, 医学系研究科, 助教 (30609756)
山口 修 大阪大学, 医学系研究科, 招へい教授 (90467580)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2019: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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| Keywords | 心不全 / 炎症 / ミトコンドリア / 心筋炎症 |
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| Outline of Final Research Achievements |
Inflammation plays an important role in the development and progression of heart failure. We investigated a molecular mechanism in the induction of sterile inflammation to find a novel therapeutic target for the treatment to heart failure. 1) We identified a microRNA that regulates the expression of DNase II, which degrades inflammatogenic mitochondrial DNA. In addition, we revealed that the microRNA is related to the pathogenesis of heart failure in a mouse heart failure model. 2) It was revealed that HMGB1 is related to the development of heart failure through the induction of inflammation. 3) We reported that an TLR9 inhibitor attenuates the development and progression of heart failure in mice, and that cytokine mRNA degradation in cardiomyocytes regulates inflammation in the heart.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで、炎症メカニズムの下流に位置するサイトカインに対する介入では心不全の予後改善効果を得られなかった。本研究では、当該microRNAとHMGB1のいずれもが心不全発症進展メカニズムの一つである無菌性炎症に関わっており、炎症メカニズムの上流に位置する分子経路への介入が心不全治療標的となり得る可能性について示した。これらの結果は、今後の新しい心不全治療戦略に繋がることが期待され、学術的にも社会的にも意義深い。
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