Molecular mechanisms of resident myogenic stem cell activation and quiescence and their possible regulation by functional food ingredients

2009 Fiscal Year Final Research Report

• Project/Area Number: 19380152
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Zootechnical science/Grassland science
• Research Institution: Kyushu University
• Principal Investigator: TATSUMI Ryuichi Kyushu University, 大学院・農学研究院, 准教授 (40250493)
• 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)
• 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
• Project Period (FY): 2007 – 2009
• 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.

Research Products

• [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 Vivo (2010)
  • Author(s): Yamada, M., Tatsumi, R., Yamanouchi, K., Hosoyama, T., Shiratsuchi, S., Sato, A., Mizunoya, W., Ikeuchi, Y., Furuse, M., Allen, R.E.
  • Journal Title: American Journal of Physiology-Cell Physiology 298 Pages: C465-C476
  • Peer Reviewed
• [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.
  • Journal Title: Journal of Biological Chemistry 285 Pages: 7111-7118
  • Peer Reviewed
• [Journal Article] In Vitro Measurement of Postnatal Changes in Proliferating Satellite Cell Frequency during Rat Muscle Growth (2010)
  • 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.
  • Journal Title: Animal Science Journal 81 Pages: 245-251
  • Peer Reviewed
• [Journal Article] Mechano-Biology of Skeletal Muscle Hypertrophy and Regeneration: Possible Mechanism of Stretch-Induced Activation of Resident Myogenic Stem Cells. (2010)
  • Author(s): Tatsumi, R.
  • Journal Title: Invited Review Animal Science Journal 81 Pages: 11-20
  • Peer Reviewed
• [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.
  • Journal Title: American Journal of Physiology-Cell Physiology 297 Pages: C238-C252
  • Peer Reviewed
• [Journal Article] Differential Expression of Sarcoplasmic and Myofibrillar Proteins of Rat Soleus Muscle during Denervation Atrophy. Bioscience (2009)
  • Author(s): Sato, Y., Shimizu, M., Mizunoya, W., Wariishi, H., Tatsumi, R., Buchman, V.L., Ikeuchi, Y.
  • Journal Title: Biotechnology and Biochemistry 73 Pages: 1748-1756
  • Peer Reviewed
• [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.
  • Journal Title: American Journal of Physiology-Cell Physiology 296 Pages: C922-C929
  • Peer Reviewed
• [Journal Article] 加齢筋萎縮の抑制:牛肉エキスに含まれる未知筋肥大因子の同定 (2009)
  • Author(s): 馬場研斗, 水野谷航, 辰巳隆一, 池内義秀, 関口健
  • Journal Title: 平成20年度食肉に関する助成研究調査成果報告書(伊藤記念財団) 27 Pages: 17-23
• [Journal Article] Protocol for High-Resolution Separation of Rodent Myosin Heavy Chain Isoforms in a Mini-Gel Electrophoresis System. (2008)
  • Author(s): Mizunoya, W., Wakamatsu, J.-I., Tatsumi, R., Ikeuchi, Y.
  • Journal Title: Analytical Biochemistry 377 Pages: 111-113
  • Peer Reviewed
• [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.
  • Journal Title: International Journal of Biochemistry and Cell Biology 40 Pages: 2183-2191
  • Peer Reviewed
• [Journal Article] Mechano-Biology of Resident Myogenic Stem Cells: Molecular Mechanism of Stretch-Induced Activation of Satellite Cells. (2008)
  • Author(s): Tatsumi, R., Allen, R.E.
  • Journal Title: Invited Review Animal Science Journal 79 Pages: 279-290
  • Peer Reviewed
• [Journal Article] 牛肉エキスに含まれる筋肥大因子に関する研究 (2008)
  • Author(s): 水野谷航, 馬場研斗, 辰巳隆一, 池内義秀, 関口 健
  • Journal Title: 平成19年度食肉に関する助成研究調査成果報告書(伊藤記念財団) 26 Pages: 22-27
• [Presentation] semaphorin3Aによる筋衛星細胞の分化促進 (2010)
  • Author(s): 鈴木貴弘, 清水直美, 山田路子, 辰巳隆一, 水野谷航, 池内義秀
  • Organizer: 第112回日本畜産学会大会
  • Place of Presentation: 明治大学駿河台キャンパス(口頭発表(形態生理))
  • Year and Date: 20100328-20100329
• [Presentation] 除神経処理を施したgamma-synuclein欠損マウスの筋組織観察 (2010)
  • Author(s): 藤竹瑞穂, 佐藤祐介, 水野谷航, 辰巳隆一, Buchman V.L., 池内義秀
  • Organizer: 第112回日本畜産学会大会
  • Place of Presentation: 明治大学駿河台キャンパス(口頭発表(形態生理))
  • Year and Date: 20100328-20100329
• [Presentation] 牛肉エキスの筋肥大作用におけるシグナル伝達経路の探索 (2009)
  • Author(s): 馬場研斗, 水野谷航, 関口健, 辰巳隆一, 池内義秀
  • Organizer: 第111回日本畜産学会大会
  • Place of Presentation: 琉球大学(口頭発表(形態生理))
  • Year and Date: 20090928-20090929
• [Presentation] 筋衛星細胞休止化へのNpn-1の関与 (2009)
  • Author(s): 山田路子, 佐藤章子, 水野谷航, 辰巳隆一, 池内義秀
  • Organizer: 第111回日本畜産学会大会
  • Place of Presentation: 琉球大学(口頭発表(形態生理))
  • Year and Date: 20090928-20090929
• [Presentation] semaphorin3Aが筋衛星細胞の分化に及ぼす影響 (2009)
  • Author(s): 鈴木貴弘, 清水直美, 山田路子, 辰巳隆一, 水野谷航, 池内義秀
  • Organizer: 第111回日本畜産学会大会
  • Place of Presentation: 琉球大学(口頭発表(形態生理))
  • Year and Date: 20090928-20090929
• [Presentation] 筋幹細胞における運動神経軸索ガイダンス因子Sema3Aの発現調節 (2009)
  • Author(s): 清水直美, 鈴木貴弘, 山田路子, 佐藤祐介, 水野谷航, 辰巳隆一, 池内義秀
  • Organizer: 第111回日本畜産学会大会
  • Place of Presentation: 琉球大学(口頭発表(形態生理))
  • Year and Date: 20090928-20090929
• [Presentation] リンゴポリフェノールの摂取が筋持久力に及ぼす影響 (2009)
  • Author(s): 宮原英生, 水野谷航, 辰巳隆一, 和賀俊明, 池内義秀
  • Organizer: 第111回日本畜産学会大会
  • Place of Presentation: 琉球大学(口頭発表(形態生理))
  • Year and Date: 20090928-20090929
• [Presentation] 筋特異的シチジンデアミナーゼAPOBEC-2の発現解析 (2009)
  • Author(s): 佐藤祐介, 水野谷航, 辰巳隆一, 池内義秀
  • Organizer: 第111回日本畜産学会大会
  • Place of Presentation: 琉球大学(口頭発表(形態生理))
  • Year and Date: 20090928-20090929
• [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
• [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
• [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
• [Presentation] 骨格筋APOBEC-2は筋線維型の変化や筋萎縮に関与している (2009)
  • Author(s): 佐藤祐介, 志水元亨, 焼山裕, 水野谷航, 辰巳隆一, 割石博之, Neuberger MS, 池内義秀
  • Organizer: 日本農芸化学会2009年度福岡大会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡)(ポスター発表(12)水野谷航)
  • Year and Date: 20090326-20090329
• [Presentation] リンゴポリフェノール摂取により骨格筋の特性が変化する (2009)
  • Author(s): 辰巳隆一
  • Organizer: 九州大学と大分県農林水産研究センター畜産試験場との試験研究連携会議
  • Place of Presentation: 大分県農林水産研究センター豊後大野管理部会議室)(口頭発表(研究シーズ紹介))
  • Year and Date: 2009-10-27
• [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
• [Presentation] 筋衛星細胞の休止化を担う複合受容体の検索 (2008)
  • Author(s): 山田路子, 佐藤祐介, 水野谷航, 辰巳隆一, 池内義秀
  • Organizer: 第109回日本畜産学会大会
  • Place of Presentation: 常磐大学(頭発表(形態生理))
  • Year and Date: 20080327-20080329
• [Presentation] 筋幹細胞は運動神経ネットワークの構築に関与する (2008)
  • Author(s): 三小田より子, 山田路子, 水野谷航, 辰巳隆一, 池内義秀
  • Organizer: 第109回日本畜産学会大会優秀発表賞応募演題
  • Place of Presentation: 常磐大学(口頭発表(形態生理))
  • Year and Date: 20080327-20080329
• [Presentation] 筋細胞の増殖・分化・成熟の各ステージにおける牛肉エキスの影響 (2008)
  • Author(s): 馬場研斗, 水野谷航, 関口健, 辰巳隆一, 池内義秀
  • Organizer: 第109回日本畜産学会大会
  • Place of Presentation: 常磐大学(口頭発表(畜産物利用))
  • Year and Date: 20080327-20080329
• [Presentation] 脂肪代謝の亢進が遅筋に特徴的な遺伝子の発現に及ぼす影響 (2008)
  • Author(s): 岩本洋平, 水野谷航, 辰巳隆一, 池内義秀
  • Organizer: 第109回日本畜産学会大会
  • Place of Presentation: 常磐大学(口頭発表(形態生理))
  • Year and Date: 20080327-20080329
• [Presentation] 骨格筋線維型と脂質代謝の関係 (2008)
  • Author(s): 水野谷航, 岩本洋平, 辰巳隆一, 池内義秀
  • Organizer: 第49回日本食肉研究会大会
  • Place of Presentation: 常磐大学(口頭発表)
  • Year and Date: 2008-03-28
• [Presentation] 除神経処理後の速筋のプロテオーム解析:遅筋との差違について (2007)
  • Author(s): 佐藤祐介, 志水元亨, 水野谷航, 辰巳隆一, 割石博之, 池内義秀
  • Organizer: 第108回日本畜産学会大会
  • Place of Presentation: 岡山大学(口頭発表(形態生理))
  • Year and Date: 20070926-20070927
• [Presentation] 卵白タンパク質が筋細胞の増殖に及ぼす影響 (2007)
  • Author(s): 田島あゆみ, 水野谷航, 辰巳隆一, 池内義秀
  • Organizer: 第108回日本畜産学会大会
  • Place of Presentation: 岡山大学(口頭発表(形態生理))
  • Year and Date: 20070926-20070927
• [Presentation] リンゴポリフェノール摂食によりラットの骨格筋線維型組成は遅筋型へシフトする (2007)
  • Author(s): 岡本慎平, 水野谷航, 和賀俊明, 辰巳隆一, 池内義秀
  • Organizer: 第108回日本畜産学会大会
  • Place of Presentation: 岡山大学(口頭発表(形態生理))
  • Year and Date: 20070926-20070927
• [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
• [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
• [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
• [Remarks] ホームページ等:
  • URL: http://hyoka.ofc.kyushuu.ac.jp/search/Details.do?method=showBasicInformation&id=K000315
• [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).
• [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
• [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