Regulation of mesenchymal cell differentiation by mechanical stress via PGC-1a

• Project/Area Number: 18680047
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Sports science
• Research Institution: The University of Tokyo
• Principal Investigator: AKIMOTO Takayuki The University of Tokyo, 大学院・医学系研究科, 講師 (00323460)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥28,600,000 (Direct Cost: ¥22,000,000、Indirect Cost: ¥6,600,000); Fiscal Year 2008: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000); Fiscal Year 2007: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000); Fiscal Year 2006: ¥12,220,000 (Direct Cost: ¥9,400,000、Indirect Cost: ¥2,820,000)
• Keywords: 筋肉 / 軟骨 / 骨 / 運動 / 細胞内シグナル伝達 / 物理的ストレス / 細胞分化 / 分化 / 細胞内カルシウム

Research Abstract

本研究では筋,骨,軟骨,脂肪などの間葉系組織の分化についてPGC-1αを中心にメカニカルストレス(物理的刺激)によるその制御を検討した.結果,メカニカルストレス誘導性の細胞内シグナル伝達経路を複数同定した.この研究を通じて,ある程度メカニカルストレス誘導性のシグナル伝達経路を特定できたことは,メカニカルストレスによって間葉系細胞の分化・成熟を制御するうえで有意義であると考えられる.研究最終年度の総括としては,研究機関3年間で,原著論文5編(加えて投稿中準備中3編),総説4編,学会発表16件,特許出願1件は十分な成果だったと考える.

Research Products

• [Journal Article] 物理刺激 (2009)
  • Author(s): 秋本崇之, 牛田多加志
  • Journal Title: 遺伝子医学MOOK別冊 (in press)掲載確定
• [Journal Article] Functional interaction of regulatory factors with the Pgc-1α promoter in response to exercise by in vivo imaging (2008)
  • Author(s): T. Akimoto, P. Li, Z. Yan
  • Journal Title: Am J Physiol Cell Physiol 295(1) Pages: 288-292
  • Peer Reviewed
• [Journal Article] Deletion of the PKA/PKG target SMTNL1 promotes an exercise-adapted phenotype in vascular smooth muscle (2008)
  • Author(s): A. A. Wooldridge, C. N. Fortner, B. Lontay, T. Akimoto, R. L. Neppl, C. Facemire, M. B. Datto, A. Kwon, E. McCook, P. Li, S. Wang, R. J. Thresher, S. E. Miller, J. Perriard, T. P. Gavin, R. C. Hickner, T. M. Coffman, A. V. Somlyo, Z. Yan, T. A. Haystead
  • Journal Title: J Biol Chem 283(17) Pages: 11850-11859
  • Peer Reviewed
• [Journal Article] Mechanical stress and tissue engineering (2008)
  • Author(s): T. Akimoto, M. Kawanishi, T. Ushida
  • Journal Title: Clin Calcium 18(9) Pages: 1313-1320
• [Journal Article] Functional interaction of regulatory factors with the Pgc-1 α promoter in response to exercise by in vivo imaging (2008)
  • Author(s): T. Akimoto, P. Li, Z. Yan
  • Journal Title: Am J Physiol Cell Physiol 295 Pages: 288-292
  • Peer Reviewed
• [Journal Article] Deletion of the PKA/PKG target SMTNL1 promotes an exercise-adapted phenotype in vascular smooth muscle (2008)
  • Author(s): A. A. Wooldridge, C. N. Fortner, B. Lontay, T. Akimoto, R. L. Neppl, C. Facemire, M. B. Datto, A. Kwon, E. McCook, P. Li , S. Wang, R. J. Thresher, S. E . Miller, J. Perriard, T. P. Gavin, R. C. Hickner, T. M. Coffman, A. V. Somlyo, Z. Yan, T. A. Haystead
  • Journal Title: J Biol Chem 23 Pages: 11850-11859
  • Peer Reviewed
• [Journal Article] Mechanical stress and tissue engineering (2008)
  • Author(s): T. Akimoto, M. Kawanishi, T. Ushida
  • Journal Title: Clin Calcium 18 Pages: 1313-1320
• [Journal Article] Deletion of the PKA/PKG target SMTNL1 promotes an exercise-adapted phenotype in vascular smc (2008)
  • Author(s): A. A. Wooldridge, C. N. Fortner, B. Lon
  • Journal Title: J Biol Chem (印刷中)(掲載確定)
  • Peer Reviewed
• [Journal Article] 骨格筋のミトコンドリア・バイオジェネシスとPGC-1α (2007)
  • Author(s): 秋本崇之, 和田正吾
  • Journal Title: 体育の科学 57(5) Pages: 345-350
• [Journal Article] Transcriptional control of the Pgc-1α gene in skeletal muscle in vivo (2007)
  • Author(s): Z. Yan, P. Li, T. Akimoto
  • Journal Title: Exerc Sport Sci Rev. Jul ; 35(3) Pages: 97-101
  • Peer Reviewed
• [Journal Article] Eccentric muscle contraction induces greater oxidative stress in skeletal muscle than concentric contraction (2007)
  • Author(s): M. Kon, K. Tanabe, F. Kimura, H. S. Lee, T. Akimoto, I. Kono
  • Journal Title: Appl Physiol, Nutrition Metabolism 32(2) Pages: 273-281
  • Peer Reviewed
• [Journal Article] Effect of Coenzyme Q10 supplementation on exercise-induced muscular injury of rats (2007)
  • Author(s): M. Kon, F. Kimura, T. Akimoto, K. Tanabe, Y. Murase, S. Ikemune, I. Kono
  • Journal Title: Exerc Immunol Rev 13 Pages: 76-88
  • Peer Reviewed
• [Journal Article] Transcriptional control of the Pgc-1α gene in skeletal muscle in vivo. (2007)
  • Author(s): Z. Yan, P. Li, T. Akimoto.
  • Journal Title: Exerc Sport Sci Rev 35 Pages: 97-101
  • Peer Reviewed
• [Journal Article] 骨格筋のミトコンドリア・バイオジェネシスとPGC-1α (2007)
  • Author(s): 秋本崇之, 和田正吾.
  • Journal Title: 体育の科学 57 Pages: 345-350
• [Journal Article] Transcriptional control of the Pgc-1α gene in skeletal muscle in vivo. (2007)
  • Author(s): Z. Yan, P. Li, T. Akimoto
  • Journal Title: Exer Sci Rev 35(3) Pages: 97-101
• [Journal Article] Eccentric muscle contraction induces greater oxidative stress in skeletal muscle than concentric contraction. (2007)
  • Author(s): M. Kon, K. Tanabe, F. Kimura, H. S. Lee, T. Akimoto, I. Kono
  • Journal Title: Appl Physiol, Nutrition Metabolism 32(2) Pages: 273-281
• [Journal Article] Resident stem cells are not required for exercise-induced fiber type-switching and angiogenesis, but required for activity-dependent muscle growth (2006)
  • Author(s): P. Li, T. Akimoto, M. Zhang, R. S. Williams, Z. Yan
  • Journal Title: Am J Physiol Cell Physiol 290(6)
  • Peer Reviewed
• [Journal Article] Resident stem cells are not required for exercise-induced fiber type-switching and angiogenesis, but required for activity-dependent muscle growth. (2006)
  • Author(s): P. Li, T. Akimoto, M. Zhang, R. S. Williams, Z. Yan.
  • Journal Title: Am J Physiol Cell Physiol 290(6) Pages: 1461-1468
• [Journal Article] 物理刺激
  • Author(s): 秋本崇之, 牛田多加志
  • Journal Title: 遺伝子医学MOOK別冊 (in press)
• [Presentation] Exercise stimulates local bioactive androgen metabolism in skeletal muscle (2008)
  • Author(s): K. Aizawa, M. Iemitsu, S. Maeda, K. Sato, T. Otsuki, T. Ushida, N. Mesaki, T. Akimoto
  • Organizer: APS Meeting Integrative Biology of Exercise
  • Place of Presentation: Hilton Head
  • Year and Date: 2008-09-27
• [Presentation] Stress responsive miR-23a attenuates skeletal muscle atrophy by targeting MAFbx/Atrogin (2008)
  • Author(s): S. Wada, Y. Kato, M. Okutsu, S. Miyaki, K. Suzuki, H. Asahara, T. Ushida, T. Akimoto
  • Organizer: APS Meeting Integrative Biology of Exercise
  • Place of Presentation: Hilton Head
  • Year and Date: 2008-09-26
• [Presentation] Functional interaction of regulatory factors with the Pgc-1α promoter in response to exercise by in vivo imaging (2008)
  • Author(s): T. Akimoto, P. Li, Z. Yan
  • Organizer: APS Meeting Integrative Biology of Exercise
  • Place of Presentation: Hilton Head
  • Year and Date: 2008-09-25
• [Presentation] Stress responsive miR-23a attenuates skeletal muscle atrophy by targe ting MAFbx /Atrogin (2008)
  • Author(s): S. Wada, Y. Kato, M. Okutsu, S. Miyaki, K. Suzuki, H. Asahara, T. Ushida, T. Akimoto
  • Organizer: APS Meeting Integrative Biology of Exercise
  • Place of Presentation: Hilton Head, SC, USA
  • Year and Date: 2008-09-25
• [Presentation] Functional interaction of regulatory factors with the Pgc-1 α promoter in response to exercise by in vivo imaging (2008)
  • Author(s): T. Akimoto, P. Li, Z. Yan
  • Organizer: APS Meeting Integrative Biology of Exercise
  • Place of Presentation: Hilton Head, SC, USA
  • Year and Date: 2008-09-25
• [Presentation] Exercise stimulates local bioactive androgen metabolism in skeletal muscle (2008)
  • Author(s): K. Aizawa, M. Iemitsu, S. Maeda, K. Sato, T. Otsuki, T. Ushida, N. Mesaki, T. Akimoto
  • Organizer: APS Meeting Integrative Biology of Exercise
  • Place of Presentation: Hilton Head, SC, USA
  • Year and Date: 2008-09-25
• [Presentation] ストレス誘導性miR-23aはatrogin-1の転写後制御を介して骨格筋萎縮を抑制する (2008)
  • Author(s): 和田正吾, 奥津光晴, 鈴木克彦, 牛田多加志, 秋本崇之
  • Organizer: 第63回日本体力医学会学術総会
  • Place of Presentation: ビーコンプラザ, 別府
  • Year and Date: 2008-09-20
• [Presentation] 筋収縮/メカニカルストレスによるPGC-1a転写活性化のメカニズム (2008)
  • Author(s): 秋本崇之, 和田正吾, 相澤勝治, 牛田多加志
  • Organizer: 第63回日本体力医学会学術総会
  • Place of Presentation: ビーコンプラザ, 別府
  • Year and Date: 2008-09-20
• [Presentation] ストレス誘導性miR-23aはatrogin-1の転写後制御を介して骨格筋萎縮を抑制する (2008)
  • Author(s): 和田正吾, 奥津光晴, 鈴木克彦, 牛田多加志, 秋本崇之
  • Organizer: 第63回日本体力医学会学術総会
  • Place of Presentation: 別府
  • Year and Date: 2008-09-19
• [Presentation] 筋収縮/メカニカルストレスによるPGC-1a転写活性化のメカニズム (2008)
  • Author(s): 秋本崇之, 和田正吾, 相澤勝治, 牛田多加志
  • Organizer: 第63回日本体力医学会学術総会
  • Place of Presentation: 別府
  • Year and Date: 2008-09-18
• [Presentation] Exercise-induced transcriptional control of PGC-1a in skeletal muscle (2008)
  • Author(s): T. Akimoto
  • Organizer: 9th Annual Meeting of Korean Association of Certificated Exercise Professionals Daegu
  • Year and Date: 2008-06-22
• [Presentation] 筋収縮/メカニカルストレスによるPGC-1a転写活性化のメカニズム (2008)
  • Author(s): 秋本崇之
  • Organizer: 名取禮二記念 筋肉の構造と機能のシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2008-03-24
• [Presentation] 筋収縮/メカニカルストレスによるPGC-1a転写活性化のメカニズム (2008)
  • Author(s): 秋本崇之
  • Organizer: 名取禮二記念筋肉の構造と機能のシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2008-03-24
• [Presentation] Mechanical stretch inhibits myoblast-to-adipocyte differentiation through Wnt signaling (2008)
  • Author(s): T. Akimoto, T. Ushida, S. Miyaki, H. Aka
  • Organizer: 54th Annual Meeting of the Orthopedic Research Society
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2008-03-02
• [Presentation] ストレッチによる脂肪分化抑制の新たな分子メカニズム (2007)
  • Author(s): 秋本崇之, 牛田多加志, 味八木茂, 赤荻博, 槌谷宏平, Z. Yan, R. S. Williams, 立石哲也
  • Organizer: 第34回日本臨床バイオメカニクス学会
  • Place of Presentation: 東京
  • Year and Date: 2007-12-07
• [Presentation] Eccentric muscle contraction induces greater oxidative stress in skeletal muscle than concentric contraction (2007)
  • Author(s): M. Kon, K. Tanabe, F. Kimura, H. S. Lee, T. Akimoto, I. Kono
  • Organizer: 8th symposium of International Society of Exercise and Immunology
  • Place of Presentation: Sendai
  • Year and Date: 2007-10-26
• [Presentation] 関節内靭帯の網羅的遺伝子発現解析 (2007)
  • Author(s): 秋本崇之, 槌谷宏平, 味八木茂, 浅原弘嗣, 牛田多加志
  • Organizer: 第62回日本体力医学会学術総会
  • Place of Presentation: 秋田
  • Year and Date: 2007-09-16
• [Presentation] ストレッチによる脂肪分化抑制の新たな分子メカニズム. シンポジウム10「生活習慣病に対する運動の効用-そのメカニズムを分子レベルで紐解く-」 (2007)
  • Author(s): 秋本崇之
  • Organizer: 第62回日本体力医学会学術総会
  • Place of Presentation: 秋田
  • Year and Date: 2007-09-15
• [Presentation] コエンザイムQ10投与が高強度運動後の酸化ストレスに及ぼす影響 (2007)
  • Author(s): 今有礼, 木村文律, 田辺解, 秋本崇之, 河野一郎
  • Organizer: 第62回日本体力医学会学術総会
  • Place of Presentation: 秋田
  • Year and Date: 2007-09-15
• [Presentation] 熱ストレスが骨格筋萎縮に与える影響 (2007)
  • Author(s): 和田正吾, 奥津光晴, 鈴木克彦, 牛田多加志, 秋本崇之
  • Organizer: 第62回日本体力医学会学術総会
  • Place of Presentation: 秋田
  • Year and Date: 2007-09-15
• [Presentation] Exercise stimulates PGC-1α transcription in skeletal muscle through activation of the p38 MAPK pathway (2006)
  • Author(s): T. Akimoto , S. C. Pohnert, P. Li, M. Zhang, C. E. Gumbs, P. B. Rosenberg, R. S. Williams, Z. Yan
  • Organizer: 14th Meeting of International Research Group of Biochemistry of Exercise
  • Place of Presentation: Seoul
  • Year and Date: 2006-10-12
• [Presentation] 骨格筋の有酸素運動適応におけるp38 MAPKの役割. シンポジウム10「分子でみる骨格筋の適応メカニズム」 (2006)
  • Author(s): 秋本崇之
  • Organizer: 第61回日本体力医学会学術総会
  • Place of Presentation: 神戸
  • Year and Date: 2006-09-24
• [Presentation] コエンザイムQ10摂取が合宿期における大学剣道選手の筋損傷と酸化ストレスに及ぼす影響 (2006)
  • Author(s): 今有礼, 田辺解, 谷村祐子, 清水和弘, 木村文律, 秋本崇之, 河野一郎
  • Organizer: 第61回日本体力医学会学術総会
  • Place of Presentation: 神戸
  • Year and Date: 2006-09-24
• [Patent(Industrial Property Rights)] 抗筋萎縮剤 (2009)
  • Inventor(s): 秋本崇之, 牛田多加志, 和田正吾
  • Industrial Property Rights Holder: 早稲田大学, 東京大学
  • Industrial Property Number: 2009-028836
  • Filing Date: 2009-02-10
• [Patent(Industrial Property Rights)] 秋本崇之, 牛田多加志, 和田正吾
  • Inventor(s): 抗筋萎縮剤
  • Industrial Property Number: 2009-028836