2023 Fiscal Year Final Research Report
Investigation of pulmonary vascular permeability based on the ROCK signaling
| Project/Area Number |
22K16175
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Oita University |
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Principal Investigator |
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| Project Period (FY) |
2022-04-01 – 2024-03-31
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| Keywords | ROCK / 血管透過性 / ARDS |
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| Outline of Final Research Achievements |
ARDS is a disease with a poor prognosis and a high mortality rate. This caused by leakage of blood components in lung cells due to increased vascular permeability due to vascular endothelial cell damage of lung. Few effective drug treatment modalities for ARDS. In this study, to elucidate the mechanism of vascular permeability regulation by ROCK, ROCK1 and ROCK2 double-conditional knockout mice, in which pulmonary vascular permeability is increased, were analyzed. The results in this study suggested that ROCK contributes to the maintenance of vascular permeability by regulating the localization of cell adhesion factors, such as VE-cadherin and β-catenin, to the pulmonary vascular endothelial cell membrane.
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| Free Research Field |
薬理学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は肺の血管透過性制御にROCKが寄与することを明らかにした。本研究で明らかとなったROCKの機能をより詳細に解析することでARDSの治療薬開発基盤を構築することが期待される。また、ARDSのみならず敗血症・浮腫・アナフィラキシーショック・がん・糖尿病網膜症など血管透過性制御機構の破綻に起因する疾患の治療法開発への貢献も期待でき、波及効果が高い。
さらに、本研究では従来の培養細胞を用いた研究により明らかとなったROCKの機能とは異なる機能が生体内で認められることを明らかにした。本研究で解析したROCK遺伝子欠損マウスはROCKの分子機能の新しい概念の創出に資することが大いに期待される。
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