| Project/Area Number |
17K09863
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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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| Research Field |
Metabolomics
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| Research Institution | Kumamoto University |
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Principal Investigator |
ISHII NORIO 熊本大学, 病院, 特任助教 (10599111)
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| Co-Investigator(Kenkyū-buntansha) |
瀬ノ口 隆文 熊本大学, 大学院生命科学研究部(医), 助教 (00530320)
近藤 龍也 熊本大学, 病院, 講師 (70398204)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 動脈硬化症 / マクロファージ / 細胞周期 / 動脈硬化 |
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| Outline of Final Research Achievements |
The presence of proliferating macrophages in the atherosclerotic lesion of atherosclerosis model mice was confirmed, and these macrophages had a high proportion of Skp2 expression.On the other hand, proliferation-suppressed macrophages showed increased ubiquitination of p27kip, whereas p27kip was less endogenously expressed in macrophages and was not altered by proliferation stimulation, but its expression was increased by induction of AMPK activity. Macrophages overexpress Skp2 in response to proliferation stimulation; stimulation by AMPK suppresses ubiquitination-mediated p27kip expression, while simultaneously increasing p27kip expression and ultimately causing G1 arrest of the cell cycle. AMPK and Skp2 may be novel therapeutic target molecules for atherosclerosis in that they suppress atherosclerosis via Mφ proliferation inhibition.
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| Academic Significance and Societal Importance of the Research Achievements |
動脈硬化における巣増殖マクロファージではユビキチンリガーゼSkp2発現が増加しており、AMPK刺激による増殖抑制は、Skp2によるp27kipユビキチン化低下に伴うp27kip発現増加を認め、最終的に細胞周期G1 arrestを誘導する可能性が示された。今回の研究を通じて動脈硬化症の発症・進展においてマクロファージのAMPK、Skp2およびp27kipが重要な役割を担っていることを明らかにした。マクロファージ増殖阻害を介して動脈硬化症の発症・進展を抑制するという新たな治療法の確立においてAMPK、Skp2およびp27kipが有力な分子標的となり得ることが証明された。
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