| Project/Area Number |
18K06703
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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 47040:Pharmacology-related
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| Research Institution | Hokkaido University of Science |
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Principal Investigator |
TAKAGURI AKIRA 北海道科学大学, 薬学部, 准教授 (90623710)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 動脈硬化 / 血管平滑筋細胞 / YAP1 / 炎症 / 内膜肥厚 / 腹部大動脈瘤 / 血管平滑筋細胞特異的YAP1ノックアウトマウス / Hippo経路 / 血管平滑筋特異的ノックアウトマウス / プラーク破綻 |
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| Outline of Final Research Achievements |
Yes-associated protein (YAP)1 is regulated by Hippo pathway, which controls cell survival and cell death in vascular smooth muscle cells. In this study, we investigated the role of YAP1 on the progression of atherosclerosis using a smooth muscle specific YAP1-KO mouse. Smooth muscle specific YAP1-KO mice showed decreased neointima formation induced by injury in carotid artery. Also, activation of YAP1 causes cell proliferation mediated by the phosphorylation of Akt in vascular smooth muscle cells. Accordingly, it suggests that YAP1 is a critical molecules for the pathogenesis of atherosclerosis.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によって、血管平滑筋細胞のYAP1が、内膜の障害により生じる内膜肥厚形成に重要な働きをすること、その機序としてAktの活性化に影響を与えることを明らかにした。本研究の成果は、YAP1が動脈硬化の形成・進展に重要な役割をもつことを示唆するものであり、これら疾患に対する新たな治療戦略を提唱に繋がる所見と考えられる。また、将来的には、YAP1の活性化と関連する疾患、がん、関節リウマチなどの疾患への応用展開に繋がることが期待される。
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