| Project/Area Number |
22K19610
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 57:Oral science and related fields
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| Research Institution | Hokkaido University |
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Principal Investigator |
HIDA Kyoko 北海道大学, 歯学研究院, 教授 (40399952)
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| Co-Investigator(Kenkyū-buntansha) |
澤 洋文 北海道大学, 人獣共通感染症国際共同研究所, 兼務教員 (30292006)
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| Project Period (FY) |
2022-06-30 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 血管内皮細胞 / 新型コロナ感染症 / 腫瘍 / 血栓症 / 好中球 / 血栓 / 感染症 |
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| Outline of Research at the Start |
SARS-CoV-2感染若齢・高齢マウスを用いて，各モデルについて感染初期と後期の2点で肺のサンプリングを行う．血管内皮細胞を単離・濃縮し，scRNAseq解析を実施する．重症化モデルと非重症化モデルの比較解析により，重症化モデルに特徴的なクラスターを同定する．さらに感染初期と後期でTrajectory解析によりクラスターの遷移状態を推定し血栓症の発症メカニズムを探る．また，肺胞上皮細胞や免疫細胞など血管内皮細胞以外の間質細胞との相互作用は，肺全体の公開scRNAseqデータとの統合解析を実施して血管内皮-間質細胞相互作用のダイナミクス，血管内皮による血栓形成促進分子機構を明らかにする．
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| Outline of Final Research Achievements |
Lungs of aged and young mice were sampled, vascular endothelial cells were isolated and enriched, and RNAseq was performed. We analysed the pathogenesis of thrombosis without characteristic of the severe disease model. For tumor endothelial cells, we isolated endothelial cells and non-endothelial cell fractions from tumors of different grades and from anti-cancer-treated mouse models using our previously established method and identified factors involved in thrombogenesis, including known factors such as vWF, P-selectin and thrombomodulin. In addition to known factors such as vWF, P-selectin and thrombomodulin, novel molecules involved in blood coagulation and immune cell migration were identified. The effects of the molecular inhibitor candidates on thrombogenesis and vasculitis were analysed histopathologically in animal models.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果により，血管内皮細胞が免疫細胞や血小板，あるいは赤血球に対する作用が明らかになった．感染症と癌における共通した血栓症発症の分子機序を明らかにした．癌患者の予後が改善する中，心血管イベント発生予防は喫緊の課題でありアンメットメディカルニーズのひとつである．新型コロナ感染症重症化に対する血栓症診断，治療法はまだ確立されておらず，本研究成果により新たな治療戦略開発ににつながるものと考えられる．
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