| Project/Area Number |
09470168
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Kyoto University |
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Principal Investigator |
SAITO Yoshihiko Kyoto Univ., Grad.Sc.of Med., Assistant Professor, 医学研究科, 助手 (30250260)
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| Co-Investigator(Kenkyū-buntansha) |
HOSODA Kiminori Kyoto Univ., Grad.Sc.of Human and Environmental Studies, Assistant Professor, 人間環境学研究科, 助手 (40271598)
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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 |
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 1998: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1997: ¥6,900,000 (Direct Cost: ¥6,900,000)
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| Keywords | endothelin-1 / cardiotrophin-1 / fibronectin / myocyte hypertrophy / カルディオトロフィン-1 / 非心筋細胞 / フィブロネクチン / 心筋肥大 / 心室筋細胞肥大 / 心室リモデリング |
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| Research Abstract |
Growing evidence indicates that the interaction of myocyte (MC) and non-MC .(NMC) occurs in the remodeling of ventricular hypertrophy. We have developed the pure MC culture and MC-NMC co-culture system to examine the involvement of endothelin-1 (ET-1), cardiotrophin-1 (CT-i) and extracellular matrix proteins, fibronectin (Fin) in the interaction.
ET-1 and CT-i mRNA were expressed mainly in NMC and much less expressed in MC.The substantial amount of ET-l and CT-i were also detected in the culture medium of the NMC culture. When MCs were co-cultured with NMC, MCs induce hypertrophic responses, such as ANP/BNP production, the increase in cell size and augmentation of protein synthesis. ETA receptor antagonist or anti-CT-1 antibody significantly suppressed the hypertrophic response in the co-culture, and the effect of BQ1 23 and anti CT-i Ab was additive in nature. These findings clearly indicate that ET-1 and CT-i are paracrine hypertrophic factors mainly secreted from NMC.We also examined the effect of Fn on MC.Fn-coating dose-dependently increased protein synthesis and ANP/BNP secretion, accompanied by FAK phosphorylation. The RGD peptide suppressed the Fin-induced hypertrophied response of MC on the pure MC and the hypertrophic response observed in the co-culture, suggesting that Fn is not merely passive participant but an active molecute in the MC hypertrophy. The present study indicates important roles of the MC-NMC interaction in the ventricular remodeling via paracrine factors and extracellular matrix proteins.
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