| Project/Area Number |
17K19689
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Internal medicine of the bio-information integration and related fields
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| Research Institution | Nippon Medical School |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
西山 功一 熊本大学, 国際先端医学研究機構, 准教授 (80398221)
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| Research Collaborator |
Yuge Shinya
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 血管新生 / 創傷治癒 / 内腔圧 / アクチン細胞骨格 / 伸展刺激 / 細胞極性 / ゼブラフィッシュ / 蛍光イメージング / アクチン重合 / 前後軸極性 / Arp2/3複合体 / 伸展張力 / 細胞運動 / メカノバイオロジー |
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| Outline of Final Research Achievements |
Fluorescence-based live-imaging of angiogenesis in wounded skin of adult zebrafish showed that elongation of the injured blood vessels was actively induced from the downstream side of blood flow, while the vessels at the upstream side only marginally elongated due to the high intravascular pressure. As the underlying mechanisms, we found that intravascular pressure induced expansion of the injured upstream vessels, which mechanically stretched the endothelial cells (ECs). Furthermore, we showed that intravascular pressure-induced stretching of ECs prevented localization of Arp2/3 actin polymerization complex at leading edge, which resulted in inhibition of actin polymerization and disruption of front-rear polarity of ECs, thereby suppressing elongation of the injured upstream vessels. Thus, this study uncovers an important role of intravascular pressure in regulation of wound angiogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
我々はこれまでゼブラフィッシュ成魚を用いた皮膚創傷治癒に伴う血管新生のライブイメージングから、「創傷時血管新生では、血流に対して下流側の損傷血管のみ伸長し、上流側の血管は内腔圧が高く伸長しない」というライブイメージングでしか知りえない現象を発見した。本研究は、この発見をもとに血管新生における内腔圧の新たな役割とそのメカニズムを明らかにした点で学術的意義がある。また、本研究成果は、内腔圧をターゲットにした新たな血管再生療法の開発など、今後の医療の発展にも寄与することが期待される。
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