The regulation of YAP activationton in endothelial cells to ameliorate septic organ damage
| Project/Area Number |
20K09287
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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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| Review Section |
Basic Section 55060:Emergency medicine-related
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| Research Institution | Shimane University |
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Principal Investigator |
Junichi Ota 島根大学, 学術研究院医学・看護学系, 助教 (50529667)
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| Co-Investigator(Kenkyū-buntansha) |
岡本 貴行 島根大学, 学術研究院医学・看護学系, 准教授 (30378286)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 敗血症 / 臓器障害 / YAP / 炎症 / 血管透過性 / 血管内皮細胞 / YAP1 / トロンボモジュリン / 血管内皮障害 |
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| Outline of Research at the Start |
播種性血管内凝固症候群（DIC）の治療薬であるトロンボモジュリンが血管内皮細胞の転写
共役因子Yes-associated protein (YAP)の活性化を抑制する可能性を見出している。
本研究では、敗血症モデルマウス、in vitro培養血管内皮細胞を用いて、
YAPの活性化を制御することで敗血症における血管透過性亢進と臓器障害が改善できるか検
証を行う。
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| Outline of Final Research Achievements |
Sepsis, is underlying endothelial dysfunction associated with excessive activation of systemic inflammation and blood coagulation, leads to multiple organ damage. In this study, we have focused on the transcription coactivator Yes-associated protein (YAP) in endothelial cells and investigated whether its activation ameliorates vascular endothelial dysfunction and multiple organ damage.
Our sepsis model mice exhibited organ damage and increased vascular permeability, but we could not evaluate YAP activation. Moreover, by using cultured vascular endothelial cells, we found that YAP activation occurs upon Lipopolysaccharides (LPS) stimulation and demonstrated that YAP is involved in the expression of inflammation-related genes.
These results indicated that septic organ damage and increased vascular permeability may be ameliorated by the regulating YAP activation in endothelial cells.
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| Academic Significance and Societal Importance of the Research Achievements |
敗血症症状や臓器障害を抑えることができる有効な治療法はなく、その開発は医学的課題である。これまで抗サイトカイン療法、抗炎症療法、抗血液凝固療法が試行されたが、十分な成果は得られていない。本研究では、血管内皮細胞のYAPの活性化制御によって敗血症時の臓器障害や血管透過性亢進が抑制できる可能性を見出した。特に、細菌由来成分や傷害関連分子パターンにより血管内皮細胞のYAPが活性化すること、また薬剤によるYAP抑制が血管内皮細胞の炎症応答を抑えることを明らかにした。これらの結果は、敗血症の新しい治療標的や治療法の開発につながると期待される。
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] The Lectin-Like Domain of Thrombomodulin Inhibits β1 Integrin-Dependent Binding of Human Breast Cancer-Derived Cell Lines to Fibronectin.2021
Author(s)
Kawamoto E, Nago N, Okamoto T, Gaowa A, Masui-Ito A, Akama Y, Darkwah S, Appiah MG, Myint PK, Obeng G, Ito A, Caidengbate S, Esumi R, Yamaguchi T, Park EJ, Imai H, Shimaoka M.
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Journal Title
Biomedicines
Volume: 9
Issue: 2
Pages: 162-162
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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