Isolation and functional analysis of a novel muscle specific gene.

• Project/Area Number: 19790526
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: University of Tsukuba (2008); Kyoto University (2007)
• Principal Investigator: OGATA Takehiro University of Tsukuba, 大学院・人間総合科学研究科, 研究員 (10402877)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,780,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: 心筋細胞 / 心不全 / 線維化 / 刺激伝導系 / 新規遺伝子 / MURC / 心肥大 / 不整脈 / ANP / RhoA

Research Abstract

新規に同定した筋特異的遺伝子Muscle-restricted coiled-coil protein (MURC)は、心筋・平滑筋細胞質内に発現しており、特に心筋細胞で高発現していた。大動脈狭窄による圧負荷刺激心肥大・心不全モデルでMURCは有意に上昇したが、MURCの心筋特異的過剰発現マウスでは心筋細胞の大小不同が存在し、加齢により心筋細胞の委縮と線維化が認められ、心機能低下と完全房室ブロックまたは心房細動が高率に認められた。さらにMURCはRhoA/ROCKシグナル経路を介してANP発現と心筋細胞でのactinの再構成の調節を行っていることも確認した。

Research Products

• [Journal Article] MURC, a muscle-restricted coiled-coil protein that modulates the Rho/ROCK pathway, induces cardiac dysfunction and conduction disturbance (2008)
  • Author(s): Ogata T, Ueyama T, Isodono K, Tagawa M, Takehara N, Kawashima T, Harada K, Takahashi T, Shioi T, Matsubara H, Oh H.
  • Journal Title: Mol Cell Biol 28(10) Pages: 3424-36
  • Peer Reviewed
• [Journal Article] MURC, a muscle-restricted coiled-coil protein, is involved in the regulation of skeletal myogenesis (2008)
  • Author(s): Tagawa M, Ueyama T, Ogata T, Takehara N, Nakajima N, Isodono K, Asada S, Takahashi T, Matsubara H, Oh H
  • Journal Title: Am J Physiol Cell Physiol 295(2)
  • Peer Reviewed
• [Journal Article] Controlled delivery of basic fibroblast growth factor promotes human cardiosphere-derived cell engraftment to enhance cardiac repair for chronic myocardial infarction (2008)
  • Author(s): Takehara N, Tsutsumi Y, Tateishi K, Ogata T, Tanaka H, Ueyama T, Takahashi T, Takamatsu T, Fukushima M, Komeda M, Yamagishi M, Yaku H, Tabata Y, Matsubara H, Oh H
  • Journal Title: J Am Coll Cardiol. 52(23) Pages: 1858-65
  • Peer Reviewed
• [Journal Article] Downregulation of Dicer expression by serum withdrawal sensitizes human endothelial cells to apoptosis (2008)
  • Author(s): Asada S, Takahashi T, Isodono K, Adachi A, Imoto H, Ogata T, Ueyama T, Matsubara H, Oh H
  • Journal Title: Am J Physiol Heart Circ Physiol 295(6)
  • Peer Reviewed
• [Journal Article] MURC, a muscle-restricted coiled-coil protein that modulates the Rho/ROCK pathway, induces cardiac dysfunction and conduction disturbance. (2008)
  • Author(s): 小形岳寛
  • Journal Title: MOLECULAR AND CELLULAR BIOLOGY 28 Pages: 3424-3436
  • Peer Reviewed
• [Journal Article] MURC, a muscle-restricted coiled-coil protein, is involved in the regulation of skeletal myogenesis. (2008)
  • Author(s): 田川雅史
  • Journal Title: The American Journal of Physiology-Cell Physiology 295
  • Peer Reviewed
• [Journal Article] Controlled delivery of basic fibroblast growth factor promotes human cardiosphere-derived cell engraftment to enhance cardiac repair for chronic myocardial infarction. (2008)
  • Author(s): 竹原尚史
  • Journal Title: The Journal of the American College of Cardiology 52 Pages: 1858-1865
  • Peer Reviewed
• [Journal Article] Downregulation of Dicer expression by serum withdrawal sensitizes human endothelial cells to apoptosis. (2008)
  • Author(s): 浅田聡
  • Journal Title: The American Journal of Physiology-Heart and Circulatory Physiology 295
  • Peer Reviewed
• [Journal Article] MURC, a muscle-restricted coiled-coil protein that modulates the Rho/ROCK pathway, induces cardiac dysfunction and conduction disturbance. (2008)
  • Author(s): T Ogata, et. al.
  • Journal Title: Mol cell Biol. (In press)
  • Peer Reviewed
• [Journal Article] Osteopontin is a myosphere-derived secretory molecule that promotes angiogenic progenitor cell proliferation through the phosphoinositide 3-kinase/Akt pathway (2007)
  • Author(s): Ogata T, Ueyama T, Nomura T, Asada S, Tagawa M, Nakamura T, Takahashi T, Matsubara H, Oh H
  • Journal Title: Biochem Biophys Res Commun 359(2) Pages: 341-7
  • Peer Reviewed
• [Journal Article] Osteopontin is a myosphere-derived secretory molecule that promotes angiogenic progenitor cell proliferation through phosphoinositide 3-kinase/Akt pathway. (2007)
  • Author(s): T Ogata, et. al.
  • Journal Title: Biochem Biophys Res Commun. 359 Pages: 341-347
  • Peer Reviewed
• [Presentation] MURC, a muscle-restricted coiled-coil protein, induces cardiomyocyte hypertrophy through the extracellular signal-regulated kinase pathway (2008)
  • Author(s): Ogata T, Ueyama T, Isodono K, Imoto H, Tagawa M, Takehara N, Asada S, Adachi A, Takahashi T, Matsubara H, Oh H
  • Organizer: AHA Basic Cardiovascular Sciences Conference
  • Place of Presentation: Keystone CO. USA
  • Year and Date: 2008-07-30
• [Presentation] MURC, a muscle-restricted coiled-coil protein, induces cardiomyocyte hypertrophy through the extracellular signal-regulated kinase pathway. (2008)
  • Author(s): 小形岳寛
  • Organizer: AHA Basic Cardiovascular Sciences Conference
  • Place of Presentation: コロラド州キーストーン
  • Year and Date: 2008-07-30
• [Presentation] A novel muscle-restricted coiled-coil protein, MURC, induces cardiac dysfunction accompanied with an altered gene expression profile (2008)
  • Author(s): Ogata T, Ueyama T, Isodono K, Tagawa M, Takehara N, Kawashima T, Shioi T, Takahashi T, Harada K, Matsubara H, Oh H
  • Organizer: 第72回日本循環器学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2008-03-29
• [Presentation] A novel muscle-restricted coiled-coil protein, MURC, induces cardiacdysfunction accompanied with an altered gene expression profile. (2008)
  • Author(s): T Ogata, et. al.
  • Organizer: 第72回日本循環器学会学術集会
  • Place of Presentation: 福岡県福岡市
  • Year and Date: 2008-03-29
• [Presentation] Osteopontin enhances proliferative self-renewal via PI3K/Akt signaling in skeletal myosphere-derived progenitor cells. (2007)
  • Author(s): T Ogata, et. al.
  • Organizer: 第11回日本心不全学会学術集会
  • Place of Presentation: 千葉県幕張市
  • Year and Date: 2007-09-10
• [Presentation] Osteopontin enhances proliferatve self-renewal via PI3K/Akt signaling in skeletal myosphere-derived progenitor cells (2007)
  • Author(s): 小形岳寛,上山知巳,野村哲也,浅田聡,田川雅史,中村智之,松原弘明,王英正
  • Organizer: 第11回日本心不全学会
  • Place of Presentation: 舞浜
  • Year and Date: 2007-09-09
• [Presentation] Secreted phosphoprotein 1 enhances proliferative self-renewal through PI3K/Akt ignaling in skeletal myosphere-derived progenitor (2007)
  • Author(s): T Ogata, et. al.
  • Organizer: The 24th Annual Meeting of ISHR Japanese Section
  • Place of Presentation: Ferrara, Italy
  • Year and Date: 2007-06-21