| Project/Area Number |
09670717
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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 | Osaka University |
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Principal Investigator |
TAKIHARA Keiko Osaka University Medical School, Assistant Professor, 医学部, 助手 (70252640)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIO Yasushi Osaka University Hospital, Medical Staff, 医学部・付属病院, 医員
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | cardiac myocyte / hypertrophy / cytoprotection / apoptosis / gp130 / cytokine |
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| Research Abstract |
Cytokines are recognized as essential mediators of normal and pathological immune responses.Recent studies have indicated the additional importance of cytokines in the pathogenesis of cardiovascular disease, especially in the idiopathic cardiomyopathy.IL-6-related cytokines share gpl3O as the signal-transducing protein.Cardiac myocyte produce various kinds of cytokines including IL-6 and cardiotrophin-1.Previously, we reported that the continuous activation of gpl3O induce myocardial hypertrophy in the transgenic mice.
In the present study, we demonstrated that the JAK/STAT, MAP kinase and PI3 kinase pathways are activated in association with the activation of gpl3O and transduce hypertrophic and cytoprotective signals in cardiac myocytes.The induction of cardiac myocyte hypertrophy was significantly amplified by STAT3 over-expression.In addition, a specific PI3 kinase inhibitor, wortmannin, completely inhibited the LIF induced activation of p70 S6 kinase and protein synthesis and partially inhibited MAP kinase activation in cardiac myocytes.LIF induced activation of Akt via PI3 kinase and increased expression of bcl-xL via STAT1, and these would partially contribute the cytoprotective effect of LIF in cardiac myocyte.Although recent investigations have addressed the participation of cytokines in various cardiovascular diseases, we have but a limited understanding of their underlying functions and mechanisms.Our investigations of the hypertrophic and cytoprotective functions of IL-6 related cytokines are expected to provide new insights into the pathophysiological significance of cytokines in the idiopathic cardiomyopathy.
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