Elucidation of diversity and universality in angiogenesis by in vivo imaging

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05125
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General physiology
• 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)
• Research Collaborator: Yuge Shinya
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 血管新生 / 創傷治癒 / 虚血 / 内皮細胞 / ペリサイト / 蛍光イメージング / ゼブラフィッシュ

Outline of Final Research Achievements

To investigate how endothelial cells (ECs) and pericytes (PCs) establish blood vessels during ischemia-induced angiogenesis, we developed a live-imaging system to analyze cutaneous angiogenesis in adult zebrafish. Cutaneous injury immediately induced angiogenesis. Tortuous and disorganized vessel networks formed within a few weeks after the injury and subsequently normalized through vessel regression in a few months. Upon injury, severed vessels elongated and anastomosed with each other. Thereafter, repaired vessels and adjacent uninjured vessels became tortuous by increasing the number of ECs. In parallel, PCs divided and migrated to cover the tortuous blood vessels. ECs sprouted from the PC-covered tortuous vessels, suggesting that EC sprouting does not require PC detachment from the vessel wall. Thus, live imaging of cutaneous angiogenesis in adult zebrafish enables us to clarify how ECs and PCs develop new blood vessels during cutaneous angiogenesis.

Free Research Field

血管生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では、創傷治癒に伴う血管新生において内皮細胞・ペリサイトが損傷部位に血管網を構築するプロセスの全貌を明らかにした。特に、血管新生におけるペリサイトの役割に関して、これまでの概念と矛盾する現象を捉え、血管新生におけるペリサイトの新たな役割を示した点で学術的な意義がある。また、癌や糖尿病網膜症では、病的な血管新生によってペリサイトの被覆が欠如した無秩序で機能的に未熟な血管が作られ病態を悪化させることから、病的血管新生が関わる疾患の病態解明、さらには治療法開発につながることが期待される。さらに、虚血性疾患などに対する効果的な血管再生療法の開発にも貢献できる。