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Molecular and Clinical Study of Renal Angiotensin and Adrenomedullin Systems

Research Project

Project/Area Number 09671049
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

MUKOYAMA Masashi  Kyoto Univ., Graduate School of Med., Assist. Professor, 医学研究科, 助手 (40270558)

Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsAT_1 receptor / AT_2 receptor / Adrenomedullin / Natriuretic peptides / Mesangium / Cell proliferation / Transgenic mouse / Hypertension / アンジオテンシンII / アドレメデュリン
Research Abstract

Cardiovascular hormones may be implicated in various renal and cardiovascular disorders such as chronic renal failure, glomerulonephritis, and hypertension. To explore their roles, we studied the renal renin-angiotensin system (RAS), adrenomedullin (AM) system, and natriuretic peptide system (NPS) using experimental disease models.
Angiotensin II type 2 (AT_2) receptor is abundantly expressed in the fetus and markedly down-regulated after birth, but reexpressed in various disease states. In cultured rat mesangial cells (MC), the AT_2 receptor was markedly induced upon confluence and exerted antiproliferative and proapoptotic effects counteracting the AT_1 receptor, and inhibited the MAP kinase cascade. Lower expression of the AT_2 receptor in glomeruli at the younger period from spontaneously hypertensive rats (SHRSP) as well as in MC of SHRSP with highly proliferative nature, suggested its implication in pathogenesis of glomerular injury and hypertension.
To clarify a role of AM as a lo … More cal regulator, we examined its secretion and action in cultured mesangial and endothelial cells (EC) using a monoclonal antibody (MAb) prepared against AM.We found secretion of AM, with a potent antigrowth property, from cultured MC as abundantly as from EC, and neutralization of endogenous AM by MAb markedly reduced basal cAMP levels and stimulated growth of EC.MC from SHRSP secreted less AM compared to WKY.These findings suggested a role of endogenous AM as an autocrine/paracrine regulator in these cells.
We have previously established the transgenic mice overexpressing brain natriuretic peptide (BNP-Tg) with low blood pressure. To assess the renal RAS-NPS interaction, we examined the effect of excess of BNP, using mouse models of renal diseases with chronic RAS activation, i.e. subtotal nephrectomy and anti-GBM nephritis. We found significant renoprotective effects of BNP, suggesting that NPS acts against RAS in vivo, perhaps at cellular and molecular levels including MAP kinase and TGF-beta expression. In another model of renal RAS activation, unilateral ureteral obstruction, renal expression of AM was significantly reduced along with development of interstitial fibrosis, suggesting that AM may normally act against renal fibrosis. Less

Report

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

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Masahisa Goto: "Growth-dependent induction of angiotensin II type 2 receptor in rat mesangial cells." Hypertension. 30(3). 358-362 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsunekazu Matsumoto: "The prostaglandin E2 and F2α receptor genes are expressed in human myometrium and are down-regulated during pregnancy." Biochemical and Biophysical Research Communications. 238(3). 838-841 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kiyoshi Mori: "Kidney-specific expression of a novel mouse organic cation ransporter-like protein." FEBS Letters. 417. 371-374 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hideo Michibata: "Autocrine/paracrine role of adrenomedullin in cultured endothelial and mesangial cells." Kidney International. 53(4). 979-985 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Numata: "Immunoradiometric assay for the N-terminal fragment of proatrial natriuretic peptide in human plasma." Clinical Chemistry. 44(5). 1008-1013 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kiyoshi Mori: "Isolation and characterization of CAXIV, a novel membrane-bound carbonic anhydrase from mouse kidney." Journal of Biological Chemistry. 274発表予定. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masahisa Goto, et al.: "Growth-dependent induction of angiotensin II type 2 receptor in rat mesangial cells." Hypertension. 30 (3). 358-362 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsunekazu Matsumoto, et al.: "The prostaglandin E2 and F2alpha receptor genes are expressed in human myometrium and are down-regulated during pregnancy." Biochem. Biophys. Res.Commun. 238 (3). 838-841 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kiyoshi Mori, et al.: "Kidney-specific expression of a novel mouse organic cation transporter-like protein." FEBS Letters. 417. 371-374 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hideo Michibata, et al.: "Autocrine/paracrine role of adrenomedullin in cultured endothelial and mesangial cells." Kidney International. 53 (4). 979-985 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Numata, et al.: "Immunoradiometric assay for the N-terminal fragment of proatrial natriuretic peptide in human plasma." Clinical Chemistry. 44 (5). 1008-1013 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kiyoshi Mori, et al.: "Isolation and characterization of CA XIV,a novel membrane-bound carbonic anhydrase from mouse kidney." Journal of Biological Chemistry. 274 (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hideo Michibata: "Autocrine/paracrine role of adrenomedullin in cultured endothelial and mesangial cells." Kidney International. 53(4). 979-985 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kiyoshi Mori: "Isolation and characterization of CA XIV,a novel membrane-bound carbonic anhydrase from mouse kidney." Journal of Biological Chemistry. 274. 発表予定 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Numata: "Immunoradiometric assay for the N-terminal fragment of proatrial natriuretic peptide in human plasma." Clinical Chemistry. 44(5). 1008-1013 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masahisa Goto: "Growth-dependent induction of angiotensin II type 2 receptor in rat mesan gial cells." Hypertension. 30(3). 358-362 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hideo Michibata: "Autocrine/paracrine role of a adrenomedullin in cultured endothelial and mesangial cells." Kidney International. 53(4)(発表予定). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kiyoshi Mori: "Kidney-specific expression of a novel mouse organic cation transporter-like protein." FEBS Letters. 417. 371-374 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsunekazu Matsumoto: "The prostaglandin E2 and F2α receptor genes are expressed in human myometrium and are down-regulated during pregnancy." Biochemical and Biophysical Research Communications. 238(3). 838-841 (1997)

    • Related Report
      1997 Annual Research Report

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

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