Elucidation of the onset mechanism of moyamoya disease by identifying pathway abnormalities

• Project/Area Number: 18K08967
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Nagoya University
• Principal Investigator: Araki Yoshio 名古屋大学, 医学部附属病院, 講師 (80467290)
• Co-Investigator(Kenkyū-buntansha): 青木 友浩 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (40633144)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: もやもや病 / 遺伝子発現解析 / マイクロアレイ / 次世代シークエンサー / パスウェイ異常

Outline of Final Research Achievements

We extracted total RNA from microarterial samples on the brain surface of patients with moyamoya disease and non-moyamoya disease, and established a protocol for comprehensive gene expression analysis using microarrays. A comparison of 11 cases of moyamoya disease and 9 cases of non-moyamoya disease revealed that 88 expression-variable genes were observed, and in pathway units, changes in genes involved in inflammation, immune response, gene repair, and oxidative phosphorylation were observed. The reproducibility of the microarray results was confirmed by performing quantitative PCR on the expression-variable genes. We believe that the findings obtained this time will be an important stepping stone for further research in the future in elucidating the pathophysiology of moyamoya disease.

Academic Significance and Societal Importance of the Research Achievements

もやもや病患者の病変部検体に対する網羅的な遺伝子発現解析はこれまで報告が無く、この点において、本研究は高い新規性を有するものと考える。また今回の実験で抽出された発現変動遺伝子の中には炎症に関わるものも多く、もやもや病の機序として炎症反応が関係しているとされる、これまでの報告を支持している。本研究の結果だけでは、これらの変化がもやもや病の原因なのか、それとも結果を反映しているかは不明であり、遺伝子の機能解析をはじめ今後更なる研究が必要と考える。