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Gene regulation and biophysiological significance of angiotensin type 2 receptor

Research Project

Project/Area Number 09470175
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKansai Medical University

Principal Investigator

MATSUBARA Hiroaki  Kansai Medical University, Associate Professor, 医学部, 講師 (10239072)

Co-Investigator(Kenkyū-buntansha) MORI Yasukiyo  Kansai Medical University, Assistant Professor, 医学部, 助手 (40268371)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 1998: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1997: ¥9,000,000 (Direct Cost: ¥9,000,000)
Keywordsangiotensin II / angiotensin II receptor / angiotensin AT2 receptor / angiotensin AT1 receptor / AT1受容体 / AT2受容体
Research Abstract

The receptors for angiotensin (Ang) II are classified into Iwo subtypes (AT1-R and AT2-R) by the discovery of non-peptidic ligands and AT1-R mediates most of the cardiovascular actions of Ang II.AT2-R is expressed at very high levels in the developing fetus, whereas in the adult its expression in the cardiovascular system is very low. The expression of AP2-R can be modulated by pathological states associated with tissue remodeling or inflammation. In failing hearts or neointima formation after vascular injury, AT2-R is re-expressed in cells proliferating in interstitial regions or neointima and exerts an inhibitory effect on Ang II-induced mitogen signals or synthesis of extracellular matrix proteins, resulting in attenuation of the tissue remodeling. An extreme way of cell growth inhibition directs cells into programmed cell death, and its process initiated by withdrawal of growth factors is also enhanced by AT2-R.Cardiac myocyte- or vascular smooth muscle-specific overexpression mice of AT2-R display an inhibitory effect on Ang II-induced chronotropic or pressor actions, suggesting the role of AT2-R on the activity of cardiac pacemaker cells or maintenance of vascular resistance. AT2-R also activates the kinin/nitric oxide/cGMP system in the cardiovascular and renal system, resulting in the AT2-R-mediated cardioprotection, vasodilation and pressure nairiuresis. These effects transmitted by AT2-R are mainly exerted by stimulation of protein tyrosine or serine/threonine phosphatases in Gi-protein dependent manner. The expression level of AT2-R is much higher in human hearts than in those of rodents, and the AT2-R-mediated actions are likely enhanced, especially by clinical application of AT1-R antagonists.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Matsubara H: "Pathophysiological roles of angiotensin II type 2 receptor in cardiovascular." Circ Res. 83.1. 1182-1191 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsubara H 他1人: "Molecular insights into angiotensin II type 1 and type 2 receptors : ..." Endocr J. 45.2. 137-150 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsubara H 他13人: "Angiotensin II type 1 receptor-induced extracellular signal-regulated protein kinase dctivation is..." Circ Res. 29.82. 1338-1348 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsubara H 他14人: "Cardiac-Specific Overexpression of Angiotensin AT2receptor causes Attenuated Response to AT1 receptor-Mediated..." J Clin Invest. 101. 527-535 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsubara H 他11人: "Angiotensin Type 2 Receptor Are Re-expressed by Cardiac Fibroblasts..." Circulation. 96. 3954-3962 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsubara H 他9人: "Mechanical Stretch induces enhanced expression of angiotensin II receptor subtypes in neonatal rat cardiac myocyt" Circ Res. 79. 887-897 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsubara H: "Pathophysiological roles of angiotensin II type2 receptor in cardiovascular and renal diseases" Circ Res (Review). 83. 1182-1191 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsubara H,Inada M: "Molecular insights into angiotensin II type 1 and type 2 receptors : expression, signaling and physiological function and clinical application of its antagonists" Endocr J (Review). 45(2). 137-50 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Murasawa S,Matsubara H,Mori Y,Nozawa Y,Gotoh N,Shibuya M,Masaki H,Maruyama K,Tsutsumi Y,Moriguchi Y,Shibazaki Y,Tanaka Y,Iwasaka T,Inada M: "Angiotensin II type 1 receptor-induced extracellular signal-regulated protein kinase activation is mediated by Ca2+/calmodulin-dependent transactivation of epidermal growth factor receptor." Circ Res. 29 ; 82. 1338-48 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masaki H,Kurihara T,Yamaki A,Inomata N,Nozawa Y,Mori Y,Murasawa S,Kizima K,Maruyama K,Horiuchi M,Dzau VJ,Takahashi H,Iwasaka T,Inada M,Matsubara H: "Cardiac-Specific Overxpression of Angiotensin AT2 receptor Causes Attenuated Response to AT1 receptor-Mediated Pressor and Chronotropic Effects" J Clin Invest. 101. 527-535 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohkubo N,Matsubara H,Nozawa Y,Mori Y,Murasawa S,Kijima K,Maruyama K,Masaki H,Tsutumi Y,Shibazaki Y,Iwasaka T,Inada M: "Angiotensin Type 2 Receptors Are Re-expressed by Cardiac Fibroblasts from Failing Myopathic Hearts and Inhibit Cell Growth and Fibrillar Collagen Metabolism" Circulation. 96. 3954-3962 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kijima K,Matsubara H,Murasawa S,Maruyama K,Mori Y,Ohkubo N,Komuro I,Yazaki Y,Iwasaka T,InadaM: "Mechanical stretch induces enhanced expression of angiotensin II receptor subtypes in neonatal rat candiac myocytes" Circ Res. 79. 887-897 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kijima K,Matsubara H,Murasawa S,Maruyama K,Ohkubo N,Mori Y,Inada M: "Regulation of angiotensin II type2 receptor gene by the protein kinase C-calcium pathway." Hypertension. 27. 529-534 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mori Y,Matsubara H,Murasawa S,Kijima K,Maruyama K,Tsukaguchi H,Okubo N,Hamakubo T,Inagami T,Iwasaka T,Inada M: "Translational regulation of angiotensin II type 1A receptor : Role of upstream AUG triplets" Hypertension. 28. 810-817 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Murasawa S,Matsubara H,Kijima K,Maruyama K,Ohkubo N,Mori Y,Iwasaka T,Inada M: "Down-regulation by cAMP of Angiotensin II Type 2 Receptor Gene Expression in PC12 cells" Hypertens Res. 19. 271-279 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nio Y,Matsubara H,Murasawa S,Kanasaki M,Inada M: "Regulation of gene transcription of angiotensin II receptor subtypes in myocardial infarction." J Clin Invest. 95. 46-54 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Murasawa S,Matsubara H,Mori Y,Kijima K,Maruyama K,Inada M: "Identification of a negative cis-regulatory element and trans-acting protein that inhibit transcription of the angiotensin II type 1a receptor gene" J Biol Chem. 270. 24282-24286 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Murasawa S., Matsubara H,Mori Y., Kijima K., Inada M: "Identification of a negative cis-regulatory element and trans-acting protein that inhibit transcription of the angiotensin II type 1a receptor gene" J Biol Chem. 270. 24282-24286 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kijima K,Matsubara H,Murasawa S,Maruyama K,Mori Y,Inada M: "Gene transcription of angiotensin II type 2 receptor is repressed by growth factors and glucocorticoids in PC12 cells" Biochem Biophs Res Commun. 216. 359-366 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Murasawa S,Matsubara H,Kanasaki M,Kijima K,Maruyama K,Nio Y,Okubo N,Tsukaguch H,Mori Y,Inada M: "Characterization of Glucocorticoid response element of rat angiotensin II type 1A receptor gene." Biochem Biophs Res Commun. 209. 832-840 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsubara H: "Pathelogical roles of angiotensin II type2 receptor in cardiovascular---" Circ Res. 83・1. 1182-1191 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tsutsumi Y 他6人: "Angiotensin II type2 receptor is upregulated in human heart with---" Circ Res. 83・10. 1035-1046 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Murasawa S 他6人: "Role of calcium-sensitive tyrosine kinase Pyk2/LAKβ/RAFTK---" Hypertension. 32・4. 668-675 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masaki H, et al: "Cardiac-specific overexpression of angiotensin II receptor causes attenuated responce to AT1 receptor-mediated pressor and chronotropic effects" J Clin Invest. 101・3. 527-535 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ohkubo N, et al: "Angiotensin type 2 receptors are reexpressed by cardiac fibroblasts from failing myopathic hamster hearts and inhibit cell gravth and fibrillar Collagen metlldism" Circulation. 96・10. 3954-3962 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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