Integrin Overexpression Improves sepsis-induced myocardial injury through attenuation of ER Stress
| Project/Area Number |
17K17047
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Emergency medicine
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| Research Institution | Gifu University |
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Principal Investigator |
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| Research Collaborator |
Ross Robert S.
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 敗血症性心筋障害 / 接着因子 / インテグリン |
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| Outline of Final Research Achievements |
Alterations in calcium homeostasis in the endoplasmic/sarcoplasmic reticulum (ER) can cause stress that ultimately may affect ventricular function. Previous report showed that α7β1D integrin modified Ca2+ regulatory pathways in the cardiomyocyte via ryanodine receptor 2 (RyR2) stabilization. In the present study, we hypothesized that integrin overexpression (OE) would have beneficial effects against sepsis-induced myocardial injury via the inhibition of ER stress.LPS injected to 9-12 week old α7β1D integrin overexpressing male mice and age/gender-matched littermate controls. These mice were sacrificed 48 hours after LPS injection.
Integrin α7β1D OE did not alter expression of Ca2+ transport proteins (SERCA2a, NCX-1 or RyR2) but did reduce RyR2 phosphorylation at serine 2808. eIF2a-P and CRT were significantly decreased in α7β1D integrin OE mice. These results suggest that α7β1D integrin OE decreases ER stress in sepsis-induced myocardial injury.
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| Academic Significance and Societal Importance of the Research Achievements |
敗血症による心機能の低下は40%-50%の患者に見られ、死亡率の悪化が示唆されている一方でその心筋障害は可逆的であり、7-10日で回復するとされており、明確な原因は解明されておらず、治療法も確立していない。
本研究において心機能障害を改善することが敗血症自体の予後を大きく変わることが確認できたため、敗血症時に心保護をすることの重要性が注目されるようになると考えられた。
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Report
(3 results)
Research Products
(7 results)
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[Journal Article] Brain-Specific Ultrastructure of Capillary Endothelial Glycocalyx and Its Possible Contribution for Blood Brain Barrier2018
Author(s)
Ando Y, Okada H, Takemura G, Suzuki K, Takada C, Tomita H, Zaikokuji R, Hotta Y, Miyazaki N, Yano H, Muraki I, Kuroda A, Fukuda H, Kawasaki Y, Okamoto H, Kawaguchi T, Watanabe T, Doi T, Yoshida T, Ushikoshi H, Yoshida S, Ogura S.
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Journal Title
Scientific Reports
Volume: 8
Issue: 1
Pages: 17523-17523
DOI
Related Report
Peer Reviewed / Open Access
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