| Project/Area Number |
15590741
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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, Health Care Center, Associate Professor, 保健センター, 助教授 (70252640)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Heart Failure / Cytokine / STAT3 / Signal transduction / Cardiac Remodeling / Cardiac Myocyte / Myocardial Injury / Apoptosis |
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| Research Abstract |
Our previous studies clearly showed that gp 130-dependent signaling pathway transduced signals directly related to cardiac myocyte survival such as induction of bcl-xL and activation of Akt. We also reported that gp 130 activation presented a protective effect on hypoxia/reoxygenation-induced cardiac myocyte damage by inducing MnSOD and scavenging ROS generation through the activation of STAT3.
Transgenic mice with cardiac specific overexpression of constitutively active form of the STAT3 gene (caSTAT3-TG) exhibited increased expression of VEGF, which was accompanied by increased capillary density in the heart. These studies suggest that gp 130/STAT signaling in cardiac myocyte can control vessel growth during cardiac remodeling. We observed that the remodeling process after acute myocardial infarction was significantly attenuated and the survival rate was significantly improved in caSTAT3-TG.
Recently, granulocyte-colony-stimulating factor (G-CSF) is suggested to improve heart failure after myocardial infarction. Our study demonstrated that G-CSF, through the receptor on cardiac myocytes, activates STAT3 and presents protective effect on cardiac myocytes, by using dominant negative form of STAT3 (dnSTAT3) transgenic mice. The beneficial effects of G-CSF on cardiac remodeling process was cancelled in dnSTAT3-TG. Signals through gp 130 provides new insights into the significance of cytokines in cardiac remodeling and activation of this pathway is proposed as a novel therapeutic strategy for the protection against pathophysiological stress.
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