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Pathophysiological analysis for tissue renin-angiotensin-system using Cre-loxP system

Research Project

Project/Area Number 16590704
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionYokohama City University (YCU)

Principal Investigator

UMEMURA Satoshi  YCU, School of Medicine, Professor, 医学部, 教授 (00128589)

Co-Investigator(Kenkyū-buntansha) FUKAMIZU Akiyoshi  Tsukuba Univ., Graduate School of Life and Environmental Sciences, Professor, 大学院生命環境科学研究科, 教授 (60199172)
KIHARA Minoru  YCU, School of Medicine, Associate Professor, 医学部, 準教授 (60177904)
TAMURA Kouichi  YCU, School of Medicine, Associate Professor, 医学部, 準教授 (40285143)
HASHIMOTO Tatsuo  YCU, School of Medicine, Assistant Professor, 医学部, 助手 (20363806)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsAngiotensinogen / Kidney / Tissue renin-angiotensin-system / Mice / 組織レニン-アンジオテンシン系
Research Abstract

Generation of loxP-franked (floxed) angiotensinogen mice.
The conditional angiotensinogen knockout construct was used to generate floxed angiotensinogen mice. Heterozygous mice were bred to generate homozygous mice.
Pathophysiological analysis of tissue renin-angiotensin-system
We examined the role of the renin-angiotensin system (RAS) in the regulation of macula densa cyclooxygenase-2 (COX-2) during altered dietary salt intake using Atg-/- mice. This study demonstrated that COX-2 activity in the macula densa can be regulated by salt intake through a mechanism independent of the RAS, and COX-2 expression is functionally linked to renal cortical N-NOS activity in Atg-/- mice (Nephron Physiol.2006).
The effects of altered dietary salt intake on renal endothelial nitric oxide synthase (eNOS) expression were determined in angiotensin type-1a receptor gene knockout (AT1a-/-) mice and Atg-/- mice. This study demonstrated that AT1a receptor-mediated inputs play critical roles in maintaining renal vascular eNOS expression and activity during changes in salt-water balance and systemic BP (J Am Soc Nephrol, 2004, Cell Tissue Res, 2006).
We examined the distribution of AT1 receptor-associated protein in nephron segments (Kidney Int,2006).
We evaluated the effect of angiotensin II on the pathogenesis of immune mediated colitis using Atg-/-. This study revealed that RAS is involved in the immune system in the colon (Gut,2005).
These results demonstrated that an antagonism of the RAS is a potential prophylactic strategy for the treatment of tissue damage.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (24 results)

All 2006 2005 2004

All Journal Article (18 results) Book (6 results)

  • [Journal Article] Expression of cyclooxygenase-2 in the juxtaglomerular apparatus of angiotensinogen gene-knockout mice.2006

    • Author(s)
      Hashimoto T, et al.
    • Journal Title

      Nephron Physiol. 102

      Pages: 1-8

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Expression of endothelial nitric oxide synthase is suppressed in the renal vasculature of angiotensinogen-gene knockout mice.2006

    • Author(s)
      Kihara M, et al.
    • Journal Title

      Cell Tissue Res. 323

      Pages: 313-320

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Interacting molecule of AT1 receptor, ATRAP, is colocalized with AT1 receptor in the mouse renal tubules.2006

    • Author(s)
      Tsurumi Y, et al.
    • Journal Title

      Kidney Int. 69

      Pages: 488-494

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Apelin stimulates myosin light chain phosphorylation in vascular smooth muscle cells.2006

    • Author(s)
      Hashimoto T, et al.
    • Journal Title

      Arterioscler Thromb Vasc Biol. 26

      Pages: 1267-1272

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Apelin stimulates myosin light chain phosphorylation in vascular smooth muscle cells.2006

    • Author(s)
      Hashimoto T, et al.
    • Journal Title

      Arterioscler Thromb Vase Biol. 26

      Pages: 1267-1272

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Transcriptional diversity and expression of NEDD4L gene in distal nephron.2006

    • Author(s)
      Umemura M, et al.
    • Journal Title

      Biochem Biophys Res Commun. 339

      Pages: 1129-1137

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Apelin stimulates myosin light chain phosphorylation in vascula smooth muscle cells.2006

    • Author(s)
      Hashimoto T, et al.
    • Journal Title

      Arterioscler Thromb Vasc Biol. (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Heparin recovers AT1 receptor and its intracellular signal transduction in cultured vascular smooth muscle cells2005

    • Author(s)
      Hashimoto T, et al.
    • Journal Title

      FEBS Lett. 579

      Pages: 281-284

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The novel angiotensin II type 1 receptor (AT1R)-associated protein ATRAP downregulates AT1R and ameliorates cardiomyocyte hypertrophy2005

    • Author(s)
      Tanaka Y, et al.
    • Journal Title

      FEBS Lett. 579

      Pages: 1579-1586

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Amelioration of 2,4,6-trinitrobenzene sulphonic acid induced colitis in angiotensinogen gene knockout mice.2005

    • Author(s)
      Inokuchi Y, et al.
    • Journal Title

      Gut 54

      Pages: 349-356

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Heparin recovers AT1 receptor and its intracellular signal transduction in cultured vascular smooth muscle cells2005

    • Author(s)
      Hashimoto T, Kihara M, et al.
    • Journal Title

      FEBS Lett. 579

      Pages: 281-284

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The novel angiotensin II type 1 receptor (AT1R)-associated protein ATRAP downregulates AT1R and ameliorates cardiomyocyte hypertrophy2005

    • Author(s)
      Tanaka Y, Tamura K, et al.
    • Journal Title

      FEBS Lett. 579

      Pages: 1579-1586

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Alterations in renal endothelial nitric oxide synthase expression by salt diet in Angiotensin type-la receptor gene knockout mice2004

    • Author(s)
      Sato K, et al.
    • Journal Title

      J Am Soc Nephrol 15

      Pages: 1756-1763

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Alterations in renal endothelial nitric oxide synthase expression by salt diet in Angiotensin type-1a receptor gene knockout mice2004

    • Author(s)
      Sato K, et al.
    • Journal Title

      J Am Soc Nephrol 15

      Pages: 1756-1763

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Alterations in renal endothelial nitric oxide synthase expression by salt diet in Angiotensin type-1a receptor gene knockout mice2004

    • Author(s)
      Sato K, Kihara M, Hashimoto T, et al.
    • Journal Title

      J Am Soc Nephrol 15

      Pages: 1756-1763

    • Related Report
      2004 Annual Research Report
  • [Journal Article] An essential role for angiotensin II type 1a receptor in pregnancy-associated hypertension with intrauterine growth retardation2004

    • Author(s)
      Saito T, Ishida J, et al.
    • Journal Title

      FASEB J. 18

      Pages: 388-390

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Nuclear receptor LXRalpha is involved in cAMP-mediated human renin gene expression2004

    • Author(s)
      Tamura K, et al.
    • Journal Title

      Mol.Cell Endocrinol. 224

      Pages: 11-20

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Regulatory Roles for APJ, a Seven-transmembrane Receptor Related to Angiotensin-type 1 Receptor in Blood Pressure in Vivo2004

    • Author(s)
      Ishida J, Hashimoto T, et al.
    • Journal Title

      J Biol.Chem. 279

      Pages: 26274-26279

    • Related Report
      2004 Annual Research Report
  • [Book] 二次性高血圧症.今日の治療指針2006年版2006

    • Author(s)
      梅村敏
    • Publisher
      医学書院
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 合併症を伴う高血圧の治療.循環器疾患最近の治療2006

    • Author(s)
      梅村敏
    • Publisher
      南江堂
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 高血圧の治療.内科学第9版2006

    • Author(s)
      梅村敏
    • Publisher
      朝倉書店(In press)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Malignant hypertension2005

    • Author(s)
      Tamura K, et al.
    • Publisher
      Nippon Rinsho
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 高血圧UP DATE、家庭血圧評価2005

    • Author(s)
      梅村敏
    • Publisher
      医歯薬出版
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] ACE inhibitors for protection against hypertensive target-organ damage2004

    • Author(s)
      Kihara M, et al.
    • Publisher
      Nippon Rinsho
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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