2022 Fiscal Year Final Research Report
Elucidation of the molecular mechanism of N-cadherin in vascular endothelial cell
Project/Area Number |
20K17131
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 53020:Cardiology-related
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Research Institution | Nippon Medical School |
Principal Investigator |
TOMORI YUJI 日本医科大学, 医学部, 講師 (30637848)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | N-cadherin / 血管透過性制御 / ゼブラフィッシュ / 蛍光イメージング / 脳血管関門(BBB) |
Outline of Final Research Achievements |
In this study, we attempted to establish endothelial cell-specific n-cadherin-deficient zebrafish in order to clarify the function of n-cadherin in the regulation of vascular permeability and the establishment and maintenance of the cerebrovascular barrier (BBB) under normal and inflammatory conditions. gene using CRISPR/Cas9 technology, but we were unable to obtain individuals in which loxP sites were inserted normally. In parallel, we also analyzed the in vivo role of Rap1, a low molecular weight G protein that enhances vascular endothelial cell-to-cell adhesion and suppresses vascular permeability. They generated and analyzed vascular endothelial cell-specific Rap1-deficient mice and found that they died from severe pulmonary edema, indicating that Rap1 is an essential molecule for the vascular barrier function of alveolar capillaries.
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Free Research Field |
循環器内科
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Academic Significance and Societal Importance of the Research Achievements |
CRISPR/Cas9の技術を用いて、内皮細胞特異的にn-cadherinを破壊することができるコンディショナルゼブラフィッシュの開発を試みたが、期待通りにloxP遺伝子を挿入でなかった。現在、挿入部位を変え、再度検討を行っている。血管透過性制御における低分子量Gタンパク質Rap1の機能に関しては、肺のバリア機能における役割を明らかにすることができた。血管内皮細胞におけるRap1の機能を解明することは、血管透過性が関わる疾患の予防法・治療法の開発に寄与する。
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