| Project/Area Number |
18K06817
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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 48010:Anatomy-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Tonami Kazuo 東京大学, 大学院医学系研究科(医学部), 助教 (70511393)
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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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 血管新生 / 血管内皮細胞 / 集団的細胞運動 / VE-カドヘリン / 回転運動 / 数理モデル / 細胞骨格 / カルパイン |
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| Outline of Final Research Achievements |
Angiogenesis is the process by which endothelial cells (ECs) form dendrite structures through sprouting, elongation, branching and lumenization. By analyzing single cell behaviors of MS-1 cells, we identified directional migration and unique fast rotational movement potentiated by cell-cell contact as a fundamental process of angiogenesis. Knockout (KO) of VE-cadherin attenuated the directional movement, whereas enhanced the rotational movement of MS-1 cells. These results suggested that VE-cadherin confers coordinated linear motility to ECs, which facilitates sprout elongation, whereas it is dispensable for the characteristic rotational movement. The rotational movement caused by VE-cadherin KO was driven by PECAM1 mediated cell adhesions and activated lamellipodial membrane ruffling and FAK activity involving the cell-cell interface, suggesting distinctive pFAK-Rac1 signal activation elicited from cell-cell interface as a possible mechanism for the rotational movement of ECs.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究における内皮細胞固有の協調動態としての回転運動の発見は、血管新生を可能にする細胞運動の素過程として、これまでの研究でも報告のない全く新しい知見である。その妥当性は、数理モデルに基づくシミュレーションにおいても、回転運動が血管に特徴的な枝状構造を効率よく再現したことでも示されている。本研究の成果を足掛かりとし、内皮細胞固有の細胞動態を生み出す責任分子の同定、さらには遺伝子の再構成実験により非血管細胞から血管構造あるいはその一部でも作ることが出来れば、血管誘導による臓器機能の再建や細胞移植による再生医療に新しい可能性を拓くことが期待される。
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