2007 Fiscal Year Final Research Report Summary
Analysis of cytokine signal repressor SOCS in the pathogenesis of heart failure
| Project/Area Number |
18590793
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kurume University |
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Principal Investigator |
YASUKAWA Hideo Kurume University, Cardiovascular Research Institute, Assistant Professor (60289361)
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| Co-Investigator(Kenkyū-buntansha) |
SUGI Yusuke Kurume University, School of Medicine, Research Associate (40389250)
MORI Takahiro Kurume University, School of Medicine, Research Associate (80389254)
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| Project Period (FY) |
2006 – 2007
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| Keywords | heart failure / cytokine / SOCS / signal transduction / gp130 |
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| Research Abstract |
The JAK/STAT pathway is an evolutionary conserved essential signaling network involved in distinct cellular process including inflammation and apoptosis. Cytokines including interferons (IFNs) and interleukins activate JAK-STAT pathway. Suppressor of cytokine signaling 1 (SOCS1) and SOCS3 are cytokine or stress-inducible inhibitors of JAK-STAT pathway. We focused on innate defense mechanisms in the cardiac myocyte that are important determinants of susceptibility to infection in viral myocarditis. Either cardiac-specific transgenic expression of SOCS1 or SOCS3 has a marked effect on the susceptibility of the heart to coxsackievirus B3 (CVB) infection; however, SOCS3 ectopic expression does not affect IFN-receptor signaling or the IFN antiviral effect in isolated myocytes. Therefore, we showed that cardiac-specific knockout of gp130 increases susceptibility to CVB, demonstrating a role for gp130 signaling via activation of STAT3. These findings suggest that endogenous SOCS3 also has significant biological effect within the cardiac myocyte. To understand physiological role of SOCS3 in the cardiac myocyte, we generated cardiac-specific SOCS3 knockout mice. The mice were born at the expected Mendelian ratio, but developed cardiac dysfunction estimated by echocardiogram from 5 months of age and died with signs of dyspnea by 8 months of age. Postmortem analysis revealed significant pleural effusions and ascites, consistent with the presence of heart failure. Histological analysis showed that the heart has a thin ventricular wall with chamber dilatation; however, typical findings of a myopathic heart such as myocyte disarray, inflammation and fibrosis were only rarely observed. Ultrastructure analysis of the dilated heart samples showed intact myofibrils, mitochondria, intercalated discs and gap junctions, suggesting that the myocyte had non-structural abnormalities that led to functional impairment.
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[Journal Article] SOCS1 protects mice against concanavalin-A-induced hepatitis by inhibiting Fas, STAT1 and JNK-mediated apoptosis2008
Author(s)
Torisu T, Nakaya M, Watanabe S, Hashimoto M, Yoshida H, Chinen T, Yoshida R, Okamoto F, Hanada T, Torisu K, akaesu G, Kobayashi T, Yasukawa H, Yoshimura A.
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Journal Title
Hepatoiogy 47
Pages: 1644-1654
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Loss of SOCS1 in helper T cells leads to defective Th17 differentiation by enhancing antagonistic effects of IFN y on STAT3 and Smads.2008
Author(s)
Tanaka K, Ichiyama K, Hashimoto M, Yoshida H, Takimoto T, Takaesu G Torisu T, Hanada T, Yasukawa H, Fukuyama S, Inoue H, Nakanishi Y, Kobayashi T, Yoshimura A:
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Journal Title
J Immunol 180
Pages: 3746-3745
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Postnatal blocking of interferon-g function prevented atherosclerotic plaque formation in apolipoprotein E-knockout mice.2007
Author(s)
Koga M, Kai H, Yasukawa H, Kato S, Yamamoto T, Kawai Y, Kusaba K, Seki Y, Kai M, Egashira K, Kataoka Y, Imaizumi T
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Journal Title
Hypertens Res 30
Pages: 259-267
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] An Innate defense mechanism against virus infection within the cardiac myocyte requiring gpl3O-STAT3 signaling.2006
Author(s)
Yajima T, Yasukawa H, Jeon ES, Xiong D, Dorner A, Iwatate M, Summers-Torres D, Jaiswal N, Hoshijima M, Chien KR, Yoshimura A, Knowlton KU.
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Journal Title
Circulation 114
Pages: 2364-2373
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Pressure overload-induced transient oxidative stress mediates perivascular inflammation and cardiac fibrosis through angiotensin II.2006
Author(s)
Kai H, Mon T, Tokuda K, Takayama N, Tahara N, Takemiya K, Kudo H, Sugi Y, Fukui D, Yasukawa H, Kuwahara F, maizumi T
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Journal Title
Hypertens Res 29
Pages: 711-718
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Transient Reduction and Activation of Circulating Dendritic cells in patients with acute decompensated heart failure.2006
Author(s)
Sugi Y, Yasukawa H, Kai H, Fukui D, Mori T, Takayama N, Tahara N, Kudo H, Takemiya , K, Koga M, Kawai Y, Imaizumi T
Organizer
The 21st Scientific Meeting of the International Society of Hypertension
Place of Presentation
Fukuoka, Japan
Year and Date
20061015-19
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Mobilization and activation of circulating dendritic cells in patients with acute myocardial infarction.2006
Author(s)
Fukui D, Yasukawa H, Sugi Y, Mori T, Takayama N, Koga M, Tahara N, Ikeda A, Futamata N, Kai H, Imaizumi T
Organizer
The American Heart Association, The 79th Scientific Sessions
Place of Presentation
Chicago, USA
Year and Date
20061012-15
Description
「研究成果報告書概要(欧文)」より
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