The role of paracrine signal networks between myocardium and endothelium in the prevention of heart failure

• Project/Area Number: 19590844
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Osaka University
• Principal Investigator: NAKAOKA Yoshikazu Osaka University, 医学系研究科, 特任助教(常勤) (90393214)
• Co-Investigator(Kenkyū-buntansha): 望月 直樹 国立循環器病センター研究所, 循環器形態部, 部長 (30311426)
• Co-Investigator(Renkei-kenkyūsha): MOCHIZUKI Naoki 国立循環器病センター研究所, 循環器形態部, 部長 (30311426)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 心不全 / 心筋-内皮相互作用 / Gab ファミリー蛋白質 / angiopoietin-1 / neuregulin-1 / 心内膜弾性繊維症 / Gabファミリー蛋白質 / 心内膜線維弾性症

Research Abstract

Neuregulin-1(NRG-1)は心臓機能維持に必須の増殖因子であるが、その作用機序の詳細は明らかではなかった。我々は、内皮細胞から分泌されるNRG-1 が心筋細胞上のErbB 受容体に作用して心筋からのAngiopoietin-1(Ang1)の分泌を誘導して、心臓組織の内皮細胞系を安定化することにより心臓の機能維持に関わることを明らかにした。そこで我々はAng1 心筋特異的欠損マウスを作成した。

Research Products

• [Journal Article] Interaction of Scaffolding Adaptor Protein Gab1 with Tyrosine Phosphatase SHP2 Negatively Regulates IGF-I-dependent Myogenic Differentiation via the ERK1/2 Signaling Pathway (2008)
  • Author(s): Koyama T¶, Nakaoka Y¶*, Fujio Y, Hirota H, Nishida K, Sugiyama S, Okamoto K, Yamauchi-Takihara K, Yoshimura M, Mochizuki S, Hori M, Hirano T, Mochizuki N.
  • Journal Title: J. Biol. Chem(*corresponding author, ¶co-firstauthor) 283 Pages: 24234-24244
  • Peer Reviewed
• [Journal Article] サイトカインシグナルによる心不全の制御機構 (2008)
  • Author(s): 瀧原圭子、中岡良和
  • Journal Title: 心臓 40 Pages: 181-186
• [Journal Article] Interaction of Scaffolding Adaptor Protein Gab1 with Tyrosine Phosphatase SHP2 Negatively Regulates IGF-I-dependent Myogenic Differentiation via the ERK1/2 Signaling Pathway (2008)
  • Author(s): Koyama T. ^*, Nakaoka Y. ^*#, et al. (^*equal contribution; #corresponding author)
  • Journal Title: Journal of Biological Chemistry 283 Pages: 24234-24244
  • Peer Reviewed
• [Journal Article] Gab family proteins are essential for postnatal maintenance of cardiac function through transmitting neuregulin-1/ErbB signaling (2007)
  • Author(s): Nakaoka Y*, Nishida K, Narimatsu M, Kamiya A, Minami T, Sawa H, Okawa K, Fujio Y, Koyama T, Maeda M, Sone M, Yamasaki S, Arai Y, Koh GY, Kodama T, Hirota H, Otsu K, Hirano T, and Mochizuki N*.
  • Journal Title: J. Clin. Invest(*co-correspondingauthor) 117 Pages: 1771-1781
  • Peer Reviewed
• [Journal Article] Gab family proteins are essential for postnatal maintenance of cardiac function via neuregulin-1/ErbB signaling (2007)
  • Author(s): Nakaoka Y., et. al.
  • Journal Title: Journal of Clinical Investigation 117 Pages: 1771-1781
  • Peer Reviewed
• [Presentation] The Novel Downstream Target of Neuregulin-1/ErbB Signaling Pathway For Maintenance of Cardiac Function (2009)
  • Author(s): Nakaoka Y.
  • Organizer: 第73回 日本循環器学会 (シンポジウム8)
  • Place of Presentation: 大阪国際会議場、大阪、日本
  • Year and Date: 2009-03-21
• [Presentation] The Novel Downstream Target of Neuregulin-1-ErbB Signaling Pathway for Maintenance of Cardiac Function~Implication for New Treatment of Heart Failure~Symposium 8 (2009)
  • Author(s): Nakaoka Y.
  • Organizer: 第73回日本循環器学会学術集会
  • Place of Presentation: 大阪
• [Presentation] Protein Gab1 is Essential for HGF-dependent Endothelial Signaling and Angiogenesis after Hindlimb Ischemia (2009)
  • Author(s): Shioyama W, Higuchi K, Hiramoto Y, Arita Y, Kuroda T, Fujio Y, Sanada F, Taniyama Y, Morishita R, Yamauchi-Takihara K, Hirano T, Hori M, Mochizuki N, and Nakaoka Y. Docking
  • Organizer: 第73回日本循環器学会学術集会
  • Place of Presentation: 大阪
• [Presentation] Scaffolding Docking Protein Gab1 Is Essential for HGF-mediated Endothelial Signaling and Angiogenesis after Hind-Limb Ischemia (2008)
  • Author(s): Shioyama W., et al.
  • Organizer: American Heart Association, Scientific Sessions 2008
  • Place of Presentation: ニューオーリンズ、ルイジアナ州、米国
  • Year and Date: 2008-11-12
• [Presentation] ドッキング蛋白質Gab1 は下肢虚血ストレス後の血管新生に必須である (2008)
  • Author(s): 中岡良和、樋口香織、塩山渉、岡本紀太郎、有田陽、黒田忠、眞田文博、谷山義明、森下竜一、藤尾慈、瀧原圭子、平野俊夫、望月直樹
  • Organizer: 第12回Molecular Cardiovascular Conference
  • Place of Presentation: 北海道余市郡赤井川村
  • Year and Date: 2008-09-05
• [Presentation] Interaction of Scaffolding Adaptor Protein Gab1 with Tyrosine Phosphatase SHP2 Negatively Regulates IGF-I-dependent Myogenic Differentiation via ERK1/2 Signaling Pathway (2008)
  • Author(s): Nakaoka Y., et al.
  • Organizer: Basic Cardiovascular Sciences Conference 2008
  • Place of Presentation: キーストン、コロラド州、米国
  • Year and Date: 2008-07-29
• [Presentation] Gab Family Scaffolding Adaptors Are Essential for Cardiac Maintenance via Transmitting Endothelial-Myocardial Crosstalk (2008)
  • Author(s): Nakaoka Y., et. al.
  • Organizer: Keystone Symposia Molecular Mechanisms of Angiogenesis in Development and Disease
  • Place of Presentation: Fairmont Hotel,バンクーバー、BC、カナダ
  • Year and Date: 2008-01-18
• [Presentation] Scaffolding Docking Protein Gab1 is Essential for HGF-dependent Endothelial Signaling and Angiogenesis after Hindlimb Ischemia (2008)
  • Author(s): Shioyama W, Higuchi K, Okamoto K, Arita Y, Sanada F, Taniyama Y, Morishita R, Kuroda T, Fujio Y, Yamauchi-Takihara K, Mochizuki N, Nakaoka Y.
  • Organizer: American Heart Association Scientific Sessions 2008
  • Place of Presentation: New Ohleans
• [Presentation] Interaction of Scaffolding Adaptor Protein Gab1 with Tyrosine Phosphatase SHP2 Negatively Regulates IGF-I-dependent Myogenic Differentiation via ERK1/2 Signaling 0Pathway (2008)
  • Author(s): Nakaoka Y, Koyama T, Okamoto K,Shioyama W, Fujio Y, Hirano T, Mochizuki N.
  • Organizer: Basic Cardiovascular Sciences Conference 2008 Heart Failure : Molecular Mechanisms and Therapeutic Targets
  • Place of Presentation: Keystone
• [Presentation] Gab Family Scaffolding Adaptors are Essential for Cardiac Maintenance via Transmitting Endothelial-Myocardial Crosstalk (2008)
  • Author(s): Nakaoka Y, and Mochizuki N.
  • Organizer: Keystone Symposia Molecular Mechanism of Angiogenesis in Development and Disease
  • Place of Presentation: Vancouver
• [Presentation] SHP2 Negatively Regulates Skeletal alpha-actin Gene Expression Downstream of LIF-dependent (2008)
  • Author(s): Shioyama W, Nakaoka Y, Fujio Y, Yamauchi-Takihara K, Mochizuki N.
  • Organizer: Hypertrophic Signaling in Cardiomyocytes ISHR Japanese Section
  • Place of Presentation: 横浜
• [Presentation] Essential role of Gab2 for Angiopoietin-1/Tie2-dependent Signaling and Cytoprotection in the Endothelial Cells (2008)
  • Author(s): Okamoto K, Shioyama W, Higuchi K, Kuroda T, Fujio Y, Yamauchi-Takihara K, Hori M, Koh GY, Mochizuki N, Nakaoka Y.
  • Organizer: 第72回日本循環器学会学術集会
  • Place of Presentation: 福岡
• [Presentation] Gab Family Scaffolding Adaptor Proteins are Essential for Postnatal Maintenance of Cardiac Fuction via Neuregulin-1/ErbB Signaling (2007)
  • Author(s): Nakaoka Y., et. al.
  • Organizer: American Heart Association, Scientific Sessions 2007
  • Place of Presentation: オーランド、フロリダ、米国
  • Year and Date: 2007-11-04
• [Presentation] 心臓組織内の心筋-内皮細胞間のサイトカインネットワークにおけるGab ファミリーアダプター蛋白質の役割 (2007)
  • Author(s): 圭吾、神谷厚範、澤洋文、小山達也、大津欣也、瀧原圭子、廣田久雄、平野俊夫、望月直樹
  • Organizer: 第11回Molecular Cardiovascular Conference
  • Place of Presentation: 北海道余市郡赤井川村
  • Year and Date: 2007-09-15
• [Presentation] Gab Family Scaffolding Adaptor Proteins are Essential for Postnatal Maintenance of Cardiac Function via Neuregulin-1/ErbB Signaling (2007)
  • Author(s): Nakaoka Y, Minami T, Sawa H, Fujio Y, Koyama T, Hirota H, Yamauchi-Takihara K, Otsu K, Hirano T, and Mochizuki N.
  • Organizer: American Heart Association Scientific Sessions 2007
  • Place of Presentation: Orlando
• [Book] サイトカインシグナルによる心不全の制御機構 (2008)
  • Author(s): 瀧原圭子、中岡良和
  • Total Pages: 5
  • Publisher: 心臟 日本心臟財団
• [Remarks] 日本循環器学会第17回八木賞を下記論文にて中岡良和が受賞した。(2008年3月)論文 : Nakaoka Y* et.al. Gab family proteins are essential for postnatal maintenance of cardiac function through transmitting neuregulin-1/ErbB signaling. J. Clin. Invest. 117 : 1771-1781, 2007
• [Remarks] 第34回佐藤賞(第73回日本循環器学会学術集会、2008 年3 月)を連携研究者の望月直樹が受賞した。タイトルは「循環器疾患病態理解のための分子イメージングによる血管内皮・心筋細胞の情報伝達解明」
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/imed3/lab_heart/
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/imed3/lab_heart/