Analysis of JunB-related cell-cell signaling for neurovascular parallel alignment

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06924
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Kanazawa Medical University
• Principal Investigator: YOSHITOMI Yasuo 金沢医科大学, 医学部, 講師 (80399039)
• Co-Investigator(Kenkyū-buntansha): 高辻 英仁 (齋藤) 金沢医科大学, 医学部, 助教 (40768959) ; 米倉 秀人 金沢医科大学, 医学部, 教授 (80240373)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 血管新生 / 脈管形成 / JunB

Outline of Final Research Achievements

In the present study, to clarify the role of JunB in the process of nerve-blood vessel parallelism, we aimed to identify molecules involved in intercellular signaling by direct nuro-vascular cell attachment and interaction using JunB activation as an indicator to elucidate the mechanism of nerve-vessel parallelism. We generated human vascular endothelial cells with a JunB promoter-reporter and used a gene activation library based on CRISPR-dCas9 for genome-wide screening the molecules that increase the activity of the JunB reporter in response to nerve-vessel contact signals. The results shows that several transcription factors and intracellular signaling molecules were identified in the JunB-induced angiogenesis pathways.

Free Research Field

血管新生

Academic Significance and Societal Importance of the Research Achievements

これまでの研究により神経ー血管並走過程でJunBが誘導されることが神経と血管の並走に必須であることが明らかとなっていたが、JunBがどのような役割を担っているのかは不明であった。神経との接触によって血管内皮細胞にJunBが誘導されるとでTip細胞に転換され血管のリモデリングが誘導される。この過程に関わるシグナル伝達分子の解明は神経との並走を介した血管ワイヤリング機構の理解に繋がり、組織再生での人工血管網の構築方法の開発につながるものと期待される。