The role of Angiopoietin-1/Tie2 signaling pathway in pulmonary arterial hypertension.

• Project/Area Number: 20790528
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Osaka University
• Principal Investigator: KURODA Tadashi Osaka University, 医学系研究科, 寄附講座助教 (60403078)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: angiopoietin-1(Ang1) / Tie2 / Gabファミリー蛋白質 / 肺高血圧症 / MAPキナーゼ / AKT / シグナル伝達 / 相補性 / angiopoietin-1 / ERK1 / 2

Research Abstract

It has been reported that angiopoietin-1(Ang1)/Tie2 signaling pathway has an essential role in the pathogenesis of pulmonary arterial hypertension (PAH). Here, we investigated the role of Gab family proteins in the Ang1/Tie2 signaling pathway. We found that both Gab1 and Gab2 have redundant roles for activation of ERK1/2 and AKT downstream of Ang1/Tie2 pathway in the endothelial cells. In addition, we have created the inducible endothelium-specific Gab1/Gab2 double knockout mice through crossing Gab1flox/flox Gab2-/- mice with VE-CadCreERT2 mice.

Research Products

• [Journal Article] SHP2 mediates gp130-dependent cardiomyocyte hypertrophy via negative regulation of skeletal alpha-actin gene (2010)
  • Author(s): Nakaoka Y, Shioyama W, Kunimoto S, Arita Y, Higuchi K, Yamamoto K, Fujio Y, Nishida K, Kuroda T, Hirota H, Yamauchi-Takihara K, Hirano T, Komuro I, Mochizuki N.
  • Journal Title: J Mol Cell Cardiol
  • Peer Reviewed
• [Journal Article] SHP2 mediates gp130-dependent cardiomyocyte hypertrophy via negative regulation of skeletal alpha-actin gene (2010)
  • Author(s): Nakaoka Y, et al.
  • Journal Title: Journal of Molecular and Cellular Cardiology (in press)
  • Peer Reviewed
• [Journal Article] Clinical significance of plasma endothelin-1 level after bosentan administration in pulmonary arterial hypertension (2009)
  • Author(s): Hiramoto Y, Shioyama W, Higuchi K, Arita Y, Kuroda T, Sakata Y, Nakaoka Y, Fujio Y, Yamauchi-Takihara K.
  • Journal Title: J Cardiol 53(3) Pages: 374-80
  • NAID: 10025183776
  • Peer Reviewed
• [Journal Article] Clinical Significance of Plasma Endothelin-1 Level after Bosentan Administration in Pulmonary Arterial Hypertension (2009)
  • Author(s): Hiramoto, et.al.
  • Journal Title: Journal of Cardiology (in press)
  • Peer Reviewed
• [Presentation] Docking 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, Nakaoka Y.
  • Organizer: 第73回日本循環器学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-21
• [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
  • 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] Accuracy and efficiency of a novel diagnusfic method for non-invasive coronary angiography using 64-slice multi-slice computed tomography (2008)
  • Author(s): 黒田忠、角辻暁、小谷順一、橘公一、辻井健一、南都伸介
  • Organizer: 第17回心血管インターベンション学会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-07-03
• [Presentation] Accuracy and Efficacy of a novel diagnostic method for non-invasive Coronary angiography using 64-slice multi-slice computed tomography (2008)
  • Author(s): Kuroda, et.al
  • Organizer: TCT Asia Pacific 2008
  • Place of Presentation: ソウル、韓国
  • Year and Date: 2008-04-24
• [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
  • Year and Date: 2008-03-28
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/cardiology/27research/2784res.html
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/cardiology/index.html
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/imed3/lab_heart/