2009 Fiscal Year Final Research Report
Molecular mechanisms of resident myogenic stem cell activation and quiescence and their possible regulation by functional food ingredients
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 |
Section | 一般 |
Research Field |
Zootechnical science/Grassland science
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Research Institution | Kyushu University |
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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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 |
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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[Journal Article] High Concentrations of HGF Inhibit Skeletal Muscle Satellite Cell Proliferation In Vitro by Inducing Expression of Myostatin: A Possible Mechanism for Re-Establishing Satellite Cell Quiescence In Vivo2010
Author(s)
Yamada, M., Tatsumi, R., Yamanouchi, K., Hosoyama, T., Shiratsuchi, S., Sato, A., Mizunoya, W., Ikeuchi, Y., Furuse, M., Allen, R.E.
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Journal Title
American Journal of Physiology-Cell Physiology 298
Pages: C465-C476
Peer Reviewed
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[Journal Article] Deficiency in APOBEC2 Leads to a Shift in Muscle Fiber Type, Diminished Body Mass and Myopathy.2010
Author(s)
Sato, Y., Probst, H.C., Tatsumi, R., Ikeuchi, Y., Neuberger, M.S., Rada, C.
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Journal Title
Journal of Biological Chemistry 285
Pages: 7111-7118
Peer Reviewed
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[Journal Article] In Vitro Measurement of Postnatal Changes in Proliferating Satellite Cell Frequency during Rat Muscle Growth2010
Author(s)
Suzuki, T., Takaishi, H., Sakata, T., Do, M.Q., Hara, M., Sato, A., Mizunoya, W., Nishimura, T, Hattori, A., Ikeuchi, Y., Tatsumi, R.
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Journal Title
Animal Science Journal 81
Pages: 245-251
Peer Reviewed
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[Journal Article] Possible Implication of Satellite Cells in Regenerative Motoneuritogenesis: HGF upregulates neural chemorepellent Sema3A during myogenic differentiation.2009
Author(s)
Tatsumi, R., Sankoda, Y., Anderson, J.E., Sato, Y., Mizunoya, W., Shimizu, N., Suzuki, T., Yamada, M., Rhoads, Jr., R.P., Ikeuchi, Y., Allen, R.E.
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Journal Title
American Journal of Physiology-Cell Physiology 297
Pages: C238-C252
Peer Reviewed
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[Journal Article] Differential Expression of Sarcoplasmic and Myofibrillar Proteins of Rat Soleus Muscle during Denervation Atrophy. Bioscience2009
Author(s)
Sato, Y., Shimizu, M., Mizunoya, W., Wariishi, H., Tatsumi, R., Buchman, V.L., Ikeuchi, Y.
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Journal Title
Biotechnology and Biochemistry 73
Pages: 1748-1756
Peer Reviewed
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[Journal Article] A Role for Calcium-Calmodulin in Regulating Nitric Oxide Production during Skeletal Muscle Satellite Cell Activation.2009
Author(s)
Tatsumi, R., Wuollet, A.L., Tabata, K., Nishimura, S., Tabata, S., Mizunoya, W., Ikeuchi, Y., Allen, R.E.
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Journal Title
American Journal of Physiology-Cell Physiology 296
Pages: C922-C929
Peer Reviewed
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[Journal Article] Matrix Metalloproteinase-2 Mediates Stretch-Induced Activation of Skeletal Muscle Satellite Cells in A Nitric Oxide Dependent Manner.2008
Author(s)
Yamada, M., Sankoda, Y., Tatsumi, R., Mizunoya, W., Ikeuchi, Y., Sunagawa, K., Allen, R.E.
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Journal Title
International Journal of Biochemistry and Cell Biology 40
Pages: 2183-2191
Peer Reviewed
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[Presentation] HGF Induces Myostatin Expression and the Subsequent Satellite Cell Quiescence in a Neuropilin-1 Dependent Manner.2009
Author(s)
Yamada, M., Tatsumi, R., Mizunoya, W., Ikeuchi, Y., Allen, R.E.
Organizer
A Joint meeting of Frontiers in Myogenesis and Skeletal Muscle Satellite and Stem Cells Alfred Lerner Hall at Columbia University
Place of Presentation
New York, NY, US
Year and Date
20090528-20090602
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[Presentation] A Possible Role for Satellite Cells in Regenerative Motoneurogenesis: HGF Up- Regulates Neural Chemorepellent Sema3A Expression.2009
Author(s)
Tatsumi, R., Sankoda, Y., Anderson, J.E., Sato, Y., Mizunoya, W., Shimizu, N., Suzuki, T., Yamada, M., Rhoads, R.P., Jr., Ikeuchi, Y., Allen, R.E.
Organizer
A Joint meeting of Frontiers in Myogenesis and Skeletal Muscle Satellite and Stem Cells Alfred Lerner Hall at Columbia University
Place of Presentation
New York, NY, US
Year and Date
20090528-20090602
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[Presentation] Skeletal Muscle Fiber Type Change and Myopathy in APOBEC-2 KO Mouse.2009
Author(s)
Sato, Y., Shimizu, M., Mizunoya, W., Tatsumi, R., Probst, H., Rada, C., Neuberger, M.S., Ikeuchi, Y.
Organizer
A Joint meeting of Frontiers in Myogenesis and Skeletal Muscle Satellite and Stem Cells Alfred Lerner Hall at Columbia University
Place of Presentation
New York, NY, US
Year and Date
20090528-20090602
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[Presentation] A Receptor Neuropilin-1 Mediates HGF-Induced Muscle Satellite Cell Quiescence.2008
Author(s)
Yamada, M., Shiratsuchi, S.-I., Tatsumi, R., Mizunoya, W., Ikeuchi, Y., Allen, R.E.
Organizer
The American Society for Cell Biology 48th Annual Meeting Moscone Center
Place of Presentation
San Francisco, CA, US
Year and Date
20081213-20081217
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[Presentation] Matrix Metalloproteinase-2 Is Involved In Mechanical Stretch-Induced Activation of Skeletal Muscle Satellite Cells.2007
Author(s)
Yamada, M., Sankoda, Y., Tatsumi, R., Mizunoya, W., Ikeuchi, Y., Allen, R.E.
Organizer
2007 FASEB Summer Research Conference on "Skeletal Muscle Satellite & Stem Cells" Oral presentation & Poster presentation, Hyatt Grand Champions
Place of Presentation
Indian Wells, CA, US(口頭発表(形態生理))
Year and Date
20070714-20070719
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[Presentation] Differential Expression of Sarcoplasmic and Myofibrillar Proteins of Rat Soleus Muscle during Denervation Atrophy.2007
Author(s)
Sato, Y., Shimizu, M., Mizunoya, W., Wariishi, H., Tatsumi, R., Ikeuchi, Y.
Organizer
Adult Skeletal Muscle Symposium: Growth, Function and Motility Indianapolis
Place of Presentation
IA, US
Year and Date
2007-06-22
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[Presentation] Food Components Do Affect Skeletal Muscle Mass and Fiber Types: Effects of Beef Extract and Apple Polyphenol.2007
Author(s)
Mizunoya, Y., Okamoto, S., Wakamatsu, J.-I., Sonoda, Y., Sekiguchi, T., Waga, T., Tatsumi, R., Ikeuchi, Y.
Organizer
Adult Skeletal Muscle Symposium: Growth, Function and Motility Indianapolis
Place of Presentation
IA, US
Year and Date
2007-06-22
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[Remarks] 2009年BBB論文賞(H22年3月)対象論文:Sato, Y., Shimizu, M., Mizunoya, W., Wariishi, H., Tatsumi, R., Buchman, V. L., and Ikeuchi, Y. Differential Expression of Sarcoplasmic and Myofibrillar Proteins of Rat Soleus Muscle during Denervation Atrophy. Bioscience, Biotechnology and Biochemistry 73, 1748-1756 (2009).
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[Remarks] 原著論文2編がEditorial Focusに選定、英文総説2編(招待)を執筆、国際学会にてTravel Award1件を受賞
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[Remarks] 2008年度日本畜産学会賞(H20年3月)受賞者:辰巳隆一受賞研究課題名:骨格筋の肥大・再生のメカノバイオロジー