| Project/Area Number |
14570677
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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 | Nagasaki University |
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Principal Investigator |
YANO Katsusuke Nagasaki University, Department of Cardiovascular Medicine, Hospital of Medicine and Dentistry, Professor, 大学院・医歯薬学総合研究科, 教授 (50039864)
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| Co-Investigator(Kenkyū-buntansha) |
SETO Hiroaki Nagasaki University, Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (00136657)
KAWANO Hiroaki Nagasaki University, Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences, Associate Professor, 医学部・歯学部附属病院, 助手 (30325659)
ASHIZAWA Naoto Nagasaki University, Department of Cardiovascular Medicine, Hospital of Medicine and Dentistry, Lecturer, 医学部・歯学部附属病院, 講師 (10301368)
YAMASHITA Shunichi Nagasaki University, Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (30200679)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Growth Hormone / Cardiac Hypertrophy / Cardiac Fibrosis / Diastolic Dysfunction / TGF-β / MAPK / Smad / Signal Transduction / ホルモン / 細胞外マトリツクス / 成量因子 |
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| Research Abstract |
This study was conducted to evaluate the chronic effect of growth hormone (GH) on cardiac geometry and function in vivo, and to determine whether GH possesses the anti-fibrotic effect in cardiac fibroblasts in vitro. GH group showed the significant increase of relative wall thickness without any disturbance of left ventricular (LV) diastolic and systolic function. GH group demonstrated the minimal fibrosis by Azan-Mallory staining, faint expression of extracellular matrix. GH down-regulated the expression of PAI-1 and fibronectin proteins activated by TGF-β. In reporter assays, OH, but not IGF-1, reduced TGF-β-specific transcriptional activity. Moreover, GH markedly down-regulated TGF-β-induced phosphorylation of p38 MAPK. These results demonstrated that a chronic excess of GH have an anti-fibrotic effect on cardiac remodeling, probably through a down-regulation of TGF-β signaling via de-phosphorylation of p38 MAPK.
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