Effect of RNF213, a moyamoya disease susceptibility gene, on blood vessels under inflammation

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K10608
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 58020:Hygiene and public health-related: including laboratory approach
• Research Institution: Mie University
• Principal Investigator: Kobayashi Hatasu 三重大学, 医学系研究科, 講師 (70542091)
• Co-Investigator(Kenkyū-buntansha): 小泉 昭夫 京都大学, 医学研究科, 名誉教授 (50124574)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: RNF213 / もやもや病 / 血管狭窄 / 炎症 / 小胞体ストレス / SEL1L

Outline of Final Research Achievements

RNF213, a susceptibility gene for moyamoya disease, markedly increases the risk of disease onset. However, the penetrance is lower than 1%, suggesting a synergistic relationship with additional environmental and genetic risk factors.
In this study, we examined the relationship between RNF213 and endoplasmic reticulum stress occurring under inflammatory conditions and found that RNF213 suppression reduces endoplasmic reticulum stress through an increase in SEL1L, which is responsible for degradation of misfolded proteins. This study indicates that RNF213 plays an important role in the regulation of endoplasmic reticulum stress and suggests that endoplasmic reticulum stress caused by inflammation may be involved in the pathogenesis of moyamoya disease.

Free Research Field

衛生学、予防医学、遺伝学

Academic Significance and Societal Importance of the Research Achievements

最近の研究で、RNF213はもやもや病に限らず多くの血管狭窄性疾患の日本人における遺伝的リスクファクターであることが知られており、RNF213変異による血管狭窄疾患の発症に関与する環境要因を特定することは予防法の開発に大きく貢献すると考えられる。本研究は、RNF213が小胞体ストレス制御に関与することを証明し、炎症等の小胞体ストレスが発生する状況が環境要因である可能性を示す社会的にも意義深いものである。