○種別 (必須): | □ | 学術論文 (審査論文)
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○言語 (必須): | □ | 英語
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○招待 (推奨): |
○審査 (推奨): |
○カテゴリ (推奨): | □ | 研究
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○共著種別 (推奨): |
○学究種別 (推奨): | □ | 博士後期課程学生による研究報告
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○組織 (推奨): | 1. | 徳島大学.疾患酵素学研究センター (2007年4月1日〜2016年3月31日/->組織[徳島大学.先端酵素学研究所.次世代酵素学研究領域])
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○著者 (必須): | 1. | (英) Pan Hai-Yan (日) (読)
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| 2. | 山田 博胤 ([徳島大学.大学院医歯薬学研究部.医学域.連携研究部門(医学域).寄附講座系(医学域).地域循環器内科学])
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| 3. | 千田 淳司 ([徳島大学.先端酵素学研究所.基幹研究部門])
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| 4. | Wang Siye
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| 5. | 矢野 仁康
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| 6. | (英) Yao Min (日) (読)
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| 7. | (英) Zhu Jianhua (日) (読)
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| 8. | 木戸 博 ([徳島大学.先端酵素学研究所.重点研究部門])
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○題名 (必須): | □ | (英) Up-regulation of ectopic trypsins in the myocardium by influenza A virus infection triggers acute myocarditis (日)
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○副題 (任意): |
○要約 (任意): | □ | (英) Influenza A virus (IAV) infection markedly up-regulates ectopic trypsins in various organs, viral envelope glycoprotein processing proteases, which are pre-requisites for virus entry and multiplication. We investigated the pathological roles of trypsin up-regulation in the progression of IAV-induced myocarditis, cytokine induction, and viral replication in the hearts, and also investigated the protective effects of trypsin inhibitor on cardiac dysfunction in vivo and selective knockdown of trypsin on IAV-induced cellular damage in cardiomyoblasts. The relationship of the expression among IAV RNA, trypsins, matrix metalloproteinase (MMP)-9, MMP-2, pro-inflammatory cytokines interleukin (IL)-6, IL-1β, and tumour necrosis factor-α was analysed in mice hearts and cardiomyoblasts after IAV infection. The severity of myocarditis was most noticeable during Day 6-9 post-infection, along with peak expression of viral RNA, trypsins, particularly trypsin , MMPs, and cytokines. Cardiac ATP levels were the lowest at Day 9. Up-regulated trypsins, viral protein, and tissue-injured loci in the myocardium were closely localized. Trypsin inhibitor aprotinin treatment in vivo and selective trypsin - and trypsin -knockdown, particularly the latter, in H9c2 cardiomyoblasts significantly suppressed viral replication, up-regulation of MMPs, and production of active MMP-9 and cytokines, resulting in marked protection against cellular damage, ATP depletion, and apoptosis. IAV infection-induced cardiac dysfunction monitored by echocardiography was improved significantly by aprotinin treatment. IAV-induced trypsins, particularly trypsin , in the myocardium trigger acute viral myocarditis through stimulation of IAV replication, proMMP-9 activation, and cytokine induction. These results suggest that up-regulation of trypsins is one of the key host pathological findings in IAV-induced myocarditis. (日)
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○キーワード (推奨): | 1. | (英) Myocarditis (日) (読)
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| 2. | トリプシン (trypsin)
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| 3. | (英) Influenza virus (日) (読)
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| 4. | 細胞質分裂 (cytokinesis)
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| 5. | (英) Matrix metalloproteases (日) (読)
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○発行所 (推奨): | □ | (英) Oxford Journals (日) (読)
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○誌名 (必須): | □ | Cardiovascular Research (European Society of Cardiology)
(pISSN: 0008-6363, eISSN: 1755-3245)
○ISSN (任意): | □ | 1755-3245
ISSN: 0008-6363
(pISSN: 0008-6363, eISSN: 1755-3245) Title: Cardiovascular researchTitle(ISO): Cardiovasc ResPublisher: Oxford University Press (NLM Catalog)
(Scopus)
(CrossRef)
(Scopus information is found. [need login])
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○巻 (必須): | □ | 89
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○号 (必須): | □ | 3
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○頁 (必須): | □ | 595 603
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○都市 (任意): |
○年月日 (必須): | □ | 西暦 2010年 10月 15日 (平成 22年 10月 15日)
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○URL (任意): |
○DOI (任意): | □ | 10.1093/cvr/cvq358 (→Scopusで検索)
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○PMID (任意): | □ | 21084314 (→Scopusで検索)
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○備考 (任意): | 1. | (英) Article.Affiliation: Division of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokushima, Tokushima 770-8503, Japan. (日)
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| 2. | (英) Article.PublicationTypeList.PublicationType: Journal Article (日)
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| 3. | (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't (日)
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| 4. | (英) OtherID: PMC3028976 (日)
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