| Project/Area Number |
16K10131
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Yokohama City University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
相原 道子 横浜市立大学, 医学研究科, 教授 (90231753)
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| Research Collaborator |
Takamura Naoko
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | カベオリン / 乾癬 / 単球・マクロファージ / 単球 / マクロファージ / 動脈硬化 / シグナル伝達 |
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| Outline of Final Research Achievements |
We have previously reported CAV-1 reduction in the epidermis of patients with psoriasis. That lead to enhanced JAK/STAT signaling and cytokine production, suggesting that aberrant CAV-1 expression may contribute to psoriatic inflammation. This study aimed to investigate whether abnormal modulation of CAV-1 on immune cells is involved in the pathogenesis of psoriasis. CAV-1 level was reduced in PBMCs from psoriasis patients and it was prominent in CD14+ monocytes. CAV-1 silencing in monocytes produced elevated levels of interleukin (IL)-1β and IL-6, and those had enhanced chemotaxis activity to MCP-1. In a murine model of psoriasis-like inflammation induced by imiquimod, significant CAV-1 reduction was also observed in PBMCs. Systemic administration of CAV-1 scaffolding domain peptide significantly improved the skin phenotype with less macrophage infiltration. Taken together, aberrant CAV-1 expression in monocytes may be involved in the pathogenesis of psoriasis.
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| Academic Significance and Societal Importance of the Research Achievements |
単球・マクロファージは、多くのサイトカインを産生するほか、動脈硬化や肥満においても中心的役割を果たす。メタボリック症候群と乾癬は合併しやすいが、単球・マクロファージは両者において重要な働きをする細胞として興味深い。今回、表皮細胞だけではなく、末梢血単球においてもCav-1発現異常が存在し、遊走能の亢進とサイトカイン産生を増強することで乾癬病態に寄与することを示した。Cav-1は脂質代謝や糖尿病病態にも強く関連していることから、全身性炎症としての乾癬にCav-1が大きく関与する可能性がある。本研究結果より、Cav-1発現異常の是正が、新たな治療標的になる可能性が示されたことに意義がある。
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