2021 Fiscal Year Final Research Report
Elucidation of opposite functions of intraluminal pressure in angiogenesis and their underlying regulatory mechanisms
| Project/Area Number |
19K22517
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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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| Review Section |
Medium-sized Section 48:Biomedical structure and function and related fields
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| Research Institution | Nippon Medical School |
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Principal Investigator |
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| Project Period (FY) |
2019-06-28 – 2022-03-31
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| Keywords | 血管新生 / 内腔圧 / 創傷治癒 / メカノセンサー / アクチン細胞骨格 / 糸球体 / 毛細血管 |
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| Outline of Final Research Achievements |
By performing fluorescence bioimaging of zebrafish, we found that during wound angiogenesis, blood flow-driven intraluminal pressure loading inhibits elongation of injured blood vessels located at sites upstream from blood flow, while downstream injured vessels actively elongate. As the underlying mechanism, we found that intraluminal pressure loading expands upstream injured vessels and stretches endothelial cells, which prevents leading edge localization of actin regulatory proteins to suppress actin polymerization, thereby inhibiting directed endothelial cell migration and vessel elongation. We also investigated the mechanism of glomerular capillary formation in zebrafish pronephros, and found during glomerular capillary formation, blood flow stabilizes their vessel structure and also induces glomerular morphogenesis possibly through blood filtration.
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| Free Research Field |
血管生物学
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| Academic Significance and Societal Importance of the Research Achievements |
血管新生は、生体恒常性維持に寄与する一方、様々な病気と関連しています。本研究により、損傷を受けた組織が修復する際に起こる血管新生の新たなメカニズムが明らかになりました。本発見は、傷の治りが遅延する疾患や虚血性疾患の新たな治療法の開発に貢献することが期待されます。また、本研究では、血液の濾過機能を有する糸球体の中に血管ができるメカニズムを研究し、血流の重要性を明らかにしました。本発見は、iPS細胞から機能的な糸球体を作り出す方法の開発に貢献することが期待されます。
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