| Project/Area Number |
19380152
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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 |
Zootechnical science/Grassland science
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| Research Institution | Kyushu University |
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Principal Investigator |
TATSUMI Ryuichi Kyushu University, 大学院・農学研究院, 准教授 (40250493)
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| Co-Investigator(Kenkyū-buntansha) |
FURUSE Mitsuhiro 九州大学, 大学院・農学研究院, 教授 (30209176)
MIZUNOYA Wataru 九州大学, 大学院・農学研究院, 助教 (20404056)
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| Research Collaborator |
ALLEN Ronald E. 米国アリゾナ大学, 教授
ANDERSON Judy E. 加国マニトバ大学, 理学部, 教授
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| Project Period (FY) |
2007 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2009: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2008: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2007: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
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| Keywords | 家畜生産システム / 食肉 / 骨格筋 / 筋肥大再生 / 筋幹細胞 / 肝細胞増殖因子(HGF) / マイオスタチン(GDF8) / 食品機能性 / 衛星細胞 / 肝細胞増殖因子HGF / マイオスタチン / マンタゴニスト / 筋肥大・再生 / 幹細胞増殖因子HGF / アンタゴニスト |
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| Research Abstract |
Skeletal muscle regeneration and work-induced hypertrophy rely on molecular events responsible for activation and quiescence of resident myogenic stem cells, satellite cells. The present studies of satellite cells in culture and in vivo demonstrated the essential role of hepatocyte growth factor (HGF) in the activation cascade of events including Ca-calmodulin complex formation, nitric oxide synthase (cNOS-1) activation, NO radical production, matrix metalloproteinase (MMP) activation, HGF release with associated extracellular segments of proteoglycans, and HGF binding to the high-affinity receptor, c-met. These experiments also revealed that HGF could induce satellite cell quiescence by stimulating myostatin expression, however, the HGF concentration required (over 10-50 ng/ml) is much higher than that for activation (2.5 ng/ml). Considering that HGF is produced by satellite cells and other cells in response to muscle damage, local concentrations of HGF bathing satellite cells may reach a threshold sufficient to induce myostatin expression. This time-lag may delay action of the negative feedback signaling in proliferating cells during initial phases of muscle regeneration, therefore, the time-coordinated increase in extracellular concentrations of HGF is a key modulator for the two contrary pathways having low and high thresholds. According to this scenario, the cell activation and quiescence may be a temporally coordinated sequence of events centering on the actions of HGF on myogenic cells. By understanding the "mechano-biology" of satellite cells, we will be able to design new procedures that specifically target activation and quiescence to enhance muscle growth and repair, contributing to the meat-animal production and human sports and health sciences aimed to enhance physical performance and medical therapies for muscular dystrophy and age-related atrophy.
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