2021 Fiscal Year Final Research Report

Mechanism and processe of stenoocclusive vascular diseases caused by RNF213 mutation in inflammatory cellular society

Planned Research

PDF

Project Area	Preventive medicine through inflammation cellular sociology
Project/Area Number	17H06397
Research Category	Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
Allocation Type	Single-year Grants
Review Section	Complex systems
Research Institution	Kyoto University
Principal Investigator	Koizumi Akio 京都大学, 医学研究科, 名誉教授 (50124574)
Co-Investigator(Kenkyū-buntansha)	S Youssefian 京都大学, 医学研究科, 教授 (00210576) 手塚徹京都大学, スーパーグローバルコース医学生命系ユニット, 特定講師 (50312319) 土生敏行武庫川女子大学, 食物栄養科学部, 准教授 (70346071) 小林果三重大学, 医学系研究科, 講師 (70542091) 原田浩二京都大学, 医学研究科, 准教授 (80452340)
Project Period (FY)	2017-06-30 – 2022-03-31
Keywords	遺伝疫学 / もやもや病 / 感受性遺伝子 / シグナル制御 / RNF213 / ER stress
Outline of Final Research Achievements	We previously identified that RNF213 is a major susceptibility gene for moyamoya disease (MMD) and its founder variant p.R4810K is a risk factor for not only MMD but also several other vascular occlusive diseases. The environmental factors and molecular mechanisms of MMD pathogenesis are largely unknown. To clarify them, in this project, we carried out epidemiological studies focusing on immunological factors in MMD, and elucidated cellular functions of RNF213. Specifically, we analyzed (1) RNF213-mediated signaling pathways involved in vascular occlusion, (2) relevance between mitotic failure and RNF213, (3) roles of RNF213 in response to endoplasmic reticulum (ER) stress, and (4) involvement of viral infection and gut microbiota in MMD pathogenesis.
Free Research Field	衛生学
Academic Significance and Societal Importance of the Research Achievements	本研究により、RNF213が炎症、アポトーシス、小胞体ストレス、細胞分裂、受容体型チロシンキナーゼなど、多様な細胞応答のシグナル制御に関わることが明らかとなった。RNF213の機能解明が進み、もやもや病をはじめとした、RNF213関連血管障害の疾患メカニズムの解明、ひいては、これらの疾患の予防・治療法の構築への貢献が期待できることに、本研究の学術的・社会的な意義がある。また、もやもや病の発症機構を理解する上で、ウィルス感染や腸内細菌叢の関与を精査したことにも意義がある。