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Molecular mechanism for transcriptional control of angiotensin II receptors

Research Project

Project/Area Number 06454294
Research Category

Grant-in-Aid for General Scientific Research (B)

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

Principal Investigator

INADA Mitsuo  Kansai Medical University, Department of Medicine, Professor, 医学部, 教授 (90115791)

Co-Investigator(Kenkyū-buntansha) MATSUBARA Hiroaki  Kansai Medical University, Department of Medicine, Associate Professor, 医学部, 講師 (10239072)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1995: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1994: ¥4,600,000 (Direct Cost: ¥4,600,000)
KeywordsAngiotensin II / Receptor / Gene / Transcription / myocyte / neuron / アルギオテンシンII / 糖質ステロイドホルモン
Research Abstract

Angiotensin II mediates vasoconstrictive and cell proliferative action through its specific receptor (AT1-R) in cardiovascular system. AT1-R expression is regulated in a cell-specific manner : the expression is abundant in vascular smooth muscle cells but very low in neurons. We examined the transcriptional mechanism of AT1-R gene and its expression profile in cardiac remodeling.
AT1-R gene consisted of three exons and third exon contains the whole open reading frame. There are three positive cis-regulatory elements and one strong negative cis-regulatory element (NRE, -489 - -331) in 5' flanking region. NRE is active only in PC12 cells but not in other cell types, such as vascular smooth muscle cells or skeletal muscle cells. Southwestern blot analyses revealed that 53KDa nuclear protein is bound to the NRE that exists in PC12 cell and brain, but not in other tissues, suggesting that this protein determines the expression pattern of AT1-R in neurons.
Expression levels of AT1-R are upregulated in hypertrophied ventricles and myocardial infarction. This regulation was mediated through gene transcription. Thus, expression of AT1-R is increased in cardiac remodeling, which suggests the effect of angiotensin II is enhanced in such pathological conditions.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] 村澤聡 他: "Identification of a negative cis-regulatory element and trans-acting protein that inhibits transcription of the angiotensinII type1a receptor gene" J Biol Chem. 270. 24282-24286 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 丹尾裕 他: "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(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 松原弘明 他: "Differential gene expression and regulation of angiotensin II receptor subtypes in rat cardiac fibroblasts and cardiomyocytes in culture" J Clin Invest. 93. 1592-1601 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 村澤聡 他: "Regulatory elements that mediate expression of the gene for the angiotensin II typela receptor for the rat" J.Biol.Chem.268. 26996-27003 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 鈴木淳一 他: "Rat angiotensin II (type 1A)receptor mRNA regulation and its subtype expression in the myocardial growth and hypertrophy" Circ Res.66. 439-447 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kizima 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
      1995 Final Research Report Summary
  • [Publications] Kizima 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
      1995 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
      1995 Final Research Report Summary
  • [Publications] Murasawa S., Matsubara H., Kijima K., Maruyama K., Mori Y., Inada M.: "Structure of the V1a vasopressin receptor gene and characterization of its promoter region and complete cDNA sequence of the 3'-end" J Biol Chem. 270. 20042-20050 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Murasawa S., Matsubara H., Kijima K., Maruyama K., Mori Y., Inada M.: "Glucocorticoids regulate V1a vasopressin receptor expression by increasing mRNA stability in vascular smooth muscle cells" Hypertension. 26. 665-669 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Murasawa S., Matsubara H., Kanasaki M., Kijima K., Maruyama K., Tsukaguchi 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
      1995 Final Research Report Summary
  • [Publications] Nio Y., Matsubara H., Murasawa S., Kanasaki M.and 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
      1995 Final Research Report Summary
  • [Publications] Matsubara H., Kanasaki M., Murasawa S., Tsukaguchi Y., Nio Y.and Inada M.: "Differential gene expression and regulation of angiotensin II receptor subtypes in rat cardiac fibroblasts and cardiomyocytes in culture" J Clin Invest. 93. 1592-1601 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Murasawa S., Matsubara H., Urakami M., and Inada M.: "Regulatory elements that mediate expression of the gene for the angiotensin II type 1a receptor for the rat" J Biol Chem. 268. 26996-27003 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 村澤聡 他: "Identification of a negative cis-regulatory element and trans-acting protein that inhibits transcription of the angiotension II type1a receptor gene" J. Biol Chem. 270. 24282-24286 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 丹尾裕 他: "Regulation of gene transcription of angiotensin II receptor subtypes in myocardial infarction" J Clin Invest. 95. 46-54 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 松原弘明 他: "Differential gene expression and regulation of angiotensin II receptor subtypes in rat cardiac fibroblasts and cardiomyocytes in culture" J Clin Invest. 93. 1592-1601 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] 村澤聡 他: "Regulatory elements that mediate expression of the gene for the angiotensin II type1a receptor for the rat" J. Biol. Chem.268. 26996-27003 (1993)

    • Related Report
      1995 Annual Research Report
  • [Publications] 鈴木淳一 他: "Rat angiotensin II (type 1A) receptor mRNA regulation and its subtype expression in the myocardial growth and hypertrophy" Circ Res.66. 439-447 (1993)

    • Related Report
      1995 Annual Research Report
  • [Publications] 村澤 聡他: "Identification of a negative cis-regulatory element and trans-acting protein that in hibits transcription of the angiotensin II typela receptor gene" J Clin Invest. (発表予定).

    • Related Report
      1994 Annual Research Report
  • [Publications] 丹尾 裕 他: "Regulation of gene transcription of angiotensin II receptor subtypes in myocardial infarction" J Clin Invest. 95. 46-54 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 松原 弘明 他: "Differential gene expression and regulation of angiotensin II receptor subtypes in rat cardiac fibroblasts and cardiomyocytes in culture" J Clin Invest. 93. 1592-1601 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 村澤 聡他: "Regulatory elements that meditate expression of the gene for the angiotensin II typela receptor for the rat" J Clin Chem.268. 26996-27003 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 鈴木 淳一他: "Rat angiotensin II (type 1A) receptor mRNA regulation and its subtype expression in the myocardial growth and hypertrophy" Circ Res.66. 439-447 (1993)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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