Elucidation of a novel regulatory mechanism of angiogenesis revealed by live imaging and its physiological significance

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19358
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 48:Biomedical structure and function and related fields
• Research Institution: Nippon Medical School
• Principal Investigator: Fukuhara Shigetomo 日本医科大学, 大学院医学研究科, 大学院教授 (70332880)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: 血管新生 / 内腔圧 / 創傷治癒 / メカニカルシグナル

Outline of Final Research Achievements

When tissues are damaged, angiogenesis is induced to repair the injury. We studied the mechanism of angiogenesis during wound healing by performing fluorescence-based live imaging of zebrafish. Our research elucidated how blood flow-driven intraluminal pressure suppresses the migration of endothelial cells in the upstream injured vessels, thereby inhibiting their elongation. Additionally, we demonstrated that TOCA family BAR proteins play a crucial role as actin-regulating proteins in endothelial cell migration during angiogenesis and further showed that these proteins also function as mechanical sensors for intraluminal pressure-induced stretching of endothelial cells to control wound angiogenesis.

Free Research Field

血管生物学

Academic Significance and Societal Importance of the Research Achievements

本研究成果をもとに、今後、内腔圧が血管新生を制御する仕組みの生理的な意義を解明することができれば、創傷治癒の遅延に関連する疾患の新たな治療法の開発、さらには心筋梗塞・狭心症、閉塞性下肢動脈硬化症などの虚血性疾患に対する効果的な血管再生療法の開発につながる可能性があります。また、本発見は、腫瘍血管新生による異常血管の形成とも関係する可能性があります。今後、この発見とがん病態との関連性が解明されれば、新たながん治療法の開発に貢献できる可能性があります。