Development of new therapeutic strategies for the treatment of atherosclerosis based on the elucidation of molecular mechanisms underlying dysregulation of signaling activity of thrombin receptor
Project/Area Number |
24591118
|
Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Circulatory organs internal medicine
|
Research Institution | Kyushu University |
Principal Investigator |
HIRANO Mayumi 九州大学, 医学(系)研究科(研究院), 助教 (80336031)
|
Co-Investigator(Kenkyū-buntansha) |
HIRANO Katsuya 香川大学, 医学部, 教授 (80291516)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Keywords | 血管内皮細胞 / 血管平滑筋細胞 / トロンビン / 受容体 / 血管透過性 / 脱感作 / トロンビン受容体 / 内皮細胞 / 平滑筋細胞 / バリアー機能障害 / 脱感作障害 / ミオシン軽鎖リン酸化 / 動脈硬化 / 平滑筋細胞A7r5 / アクチン繊維束 / 受容体発現亢進 |
Outline of Final Research Achievements |
The present research project yielded the following achievements regarding the role of thrombin receptor in the pathogenesis and progression of atherosclerosis:1. Thrombin receptor PAR1 induces the phosphorylation of myosin light chain, thereby increasing the permeability of endothelial cells. 2. The di-phosphorylation of myosin light chain and the actin filament formation at the cell periphery play a key role for the increase in endothelial permeability. 3. The present research established the cellular model, in which the desensitization mechanism for the thrombin receptor is impaired. Namely, the cells exhibited sustained, repetitive and irreversible response to thrombin receptor agonists. These phenomenon are indicators for impairment of receptor desensitization. 4. Oxidative stress and extracellular signal-regulated protein kinase (ERK) play a critical role for the impairment of receptor desensitization.
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Report
(4 results)
Research Products
(21 results)