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Translational research and clinical application of the natriuretic peptide system in the kidney.

Research Project

Project/Area Number 20590956
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionKyoto University

Principal Investigator

MUKOYAMA Masashi  Kyoto University, 医学研究科, 准教授 (40270558)

Co-Investigator(Renkei-kenkyūsha) MORI Kiyoshi  京都大学, 医学研究科, 特定准教授 (60343232)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords腎臓学 / 慢性賢臓病 / トランスレーショナルリサーチ / Na利尿ペプチド / ノックアウトマウス / アルドステロン / 糖尿病性賢症 / 蛋白尿 / ポドサイト / 慢性腎臓病 / トランスジェニックマウス / 糖尿病性腎症 / 結合組織成長因子(CTGF) / 線維化
Research Abstract

Natriuretic peptide family (ANP, BNP, and CNP) exert potent diuretic, natriuretic and vasorelaxing properties, as well as the inhibition of the renin-angiotensin-aldosterone system. We investigated the role of natriuretic peptides in renal disease and its complications.
1. Preparation of CNP-transgenic mice (CNP-Tg) and effects of CNP on renal injury :
CNP acts as a local hormone in the vessel, bone and kidney. Human SAP promoter-driven CNP-Tg exhibited enhanced bone growth as a result of excess circulating CNP. CNP-Tg showed ameliorated renal fibrosis and macrophage infiltration upon obstructive nephropathy model.
2. Role of GC-A (a receptor for ANP and BNP) and aldosterone in glomerular injury :
GC-A is expressed abundantly in renal tubules, but its role in glomerular injury is unknown. When GC-A knockout mice were subjected to aldosterone and high salt, massive proteinuria with marked podocyte injury was observed, which was alleviated with the MR antagonist, ARB or antioxidant.
3. Role of ANP and BNP in peritoneal sclerosis :
Peritoneal sclerosis is a serious complication in chronic peritoneal dialysis, but the effective treatment is not established yet. Subcutaneous ANP administration as well as chronic BNP excess in transgenic mice effectively ameliorated peritoneal adhesion in a mouse model of peritoneal sclerosis.
These results indicate that natriuretic peptides will have a various therapeutic potential in renal disease and related pathophysiological conditions.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (29 results)

All 2010 2009 2008 Other

All Journal Article (18 results) (of which Peer Reviewed: 18 results) Presentation (9 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Circulating C-type natriuretic peptide (CNP) rescues chondrodysplastic CNP knockout mice from their impaired skeletal growth and early death.2010

    • Author(s)
      Fujii T, Komatsu Y, Yasoda A, Kondo E, Yoshioka T, Nambu T, Kanamoto N, Miura M, Tamura N, Arai H, Mukoyama M, Nakao K
    • Journal Title

      Endocrinology 151

      Pages: 4381-4388

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Podocyte-specific expression of tamoxifeninducible Cre recombinase in mice.2010

    • Author(s)
      Yokoi H, Kasahara M, Mukoyama M, Mori K, Kuwahara K, Fujikura J, Arai Y, Saito Y, Ogawa Y, Kuwabara T, Sugawara A, Nakao K.
    • Journal Title

      Nephrol Dial Transplant 25

      Pages: 2120-2124

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Circulating C-type natriuretic peptide (CNP) rescues chondrodysplastic CNP knockout mice from their impaired skeletal growth and early death.2010

    • Author(s)
      Toshihito Fujii, et al.
    • Journal Title

      Endocrinology

      Volume: 151 Pages: 4381-4388

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Podocyte-specific expression of tamoxifen-inducible Cre recombinase in mice.2010

    • Author(s)
      Hideki Yokoi, et al.
    • Journal Title

      Nephrology, Dialysis and Transplantation

      Volume: 25 Pages: 2120-2124

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Searching for novel intercellular signal-transducing molecules in the kidney and their clinical application.2010

    • Author(s)
      Kiyoshi Mori, et al.
    • Journal Title

      Clinical and Experimental Nephrology

      Volume: 14 Pages: 523-527

    • NAID

      10029321075

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of left ventricular hypertrophy on the time-course of renal function in hypertensive patients : A subanalysis of the CASE-J trial.2010

    • Author(s)
      Kenji Ueshima, et al.
    • Journal Title

      Circulation Journal

      Volume: 74 Pages: 2132-2138

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Podocyte-specific expression of tamoxifen-inducible Cre recombinase in mice.2010

    • Author(s)
      Hideki Yokoi, et al.
    • Journal Title

      Nephrology, Dialysis and Transplantation 25(印刷中)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Translational research of novel hormones : Lessons from animal models and rare human diseases to common human diseases.2009

    • Author(s)
      Nakao K, Yasoda A, Ebihara K, Hosoda K, Mukoyama M
    • Journal Title

      J Mol Med 87

      Pages: 1029-1039

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chronically elevated plasma C-type natriuretic peptide level stimulates skeletal growth in transgenic mice.2009

    • Author(s)
      Kake T, Kitamura H, Adachi Y, Yoshioka T, Watanabe T, Matsushita H, Fujii T, Kondo E, Tachibe T, Kawase Y, Jishage K, Yasoda A, Mukoyama M, Nakao K
    • Journal Title

      Am J Physiol Endocr Metab 297

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reduction in urinary excretion of neutrophil gelatinase-associated lipocalin by angiotensin receptor blockers in hypertensive patients.2009

    • Author(s)
      Kasahara M, Mori K, Satoh N, Kuwabara T, Yokoi H, Shimatsu A, Sugawara A, Mukoyama M, Nakao K
    • Journal Title

      Nephrol Dial Transplant 24

      Pages: 2608-2609

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Urinary neutrophil gelatinase-associated lipocalin levels reflect damage to glomeruli, proximal tubules, and distal nephrons.2009

    • Author(s)
      Kuwabara T, Mori K, Mukoyama M, Kasahara M, Yokoi H, Saito Y, Yoshioka T, Ogawa Y, Imamaki H, Kusakabe T, Ebihara K, Omata M, Satoh N, Sugawara A, Barasch J, Nakao K
    • Journal Title

      Kidney Int 75

      Pages: 285-294

    • NAID

      120005678177

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chronically elevated plasma C-type natriuretic peptide level stimulates skeletal growth in transgenic mice.2009

    • Author(s)
      Takei Kake, et al.
    • Journal Title

      American Journal of Physiology Endocrinology and Metabolism 297

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Translational research of novel hormones : Lessons from animal models and rare human diseases to common human diseases.2009

    • Author(s)
      Kazuwa Nakao, et al.
    • Journal Title

      Journal of Molecular Medicine 87

      Pages: 1029-1039

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduction in urinary excretion of neutrophil gelatinase-associated lipocalin by angiotensin receptor blockers in hypertensive patients.2009

    • Author(s)
      Masato Kasahara, et al.
    • Journal Title

      Nephrology, Dialysis and Transplantation 24

      Pages: 2608-2609

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Urinary neutrophil gelatinase-associated lipocalin levels reflect damage to gelomeruli, proximal tubules, and distal nephrons.2009

    • Author(s)
      Takashige Kuwabara, et al.
    • Journal Title

      Kidney International 75

      Pages: 285-294

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adrenomedullin inhibits connective tissue growth factor expression, extracellular signal- regulated kinase activation and renal fibrosis.2008

    • Author(s)
      Nagae T, Mori K, Mukoyama M, Kasahara M, Yokoi H, Suganami T, Sawai K, Yoshioka T, Koshikawa M, Saito Y, Ogawa Y, Kuwabara T, Tanaka I, Sugawara A, Kuwahara T, Nakao K
    • Journal Title

      Kidney Int 74

      Pages: 70-80

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of connective tissue growth factor in podocytes worsens diabetic neohropathy in mice.2008

    • Author(s)
      Hideki Yokoi, et al.
    • Journal Title

      Kidney International 73

      Pages: 446-455

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adrenomedullin inhibits connective tissue growth factor expression, extracellular signal-regulated kinase activation and renal fibrosis.2008

    • Author(s)
      Tetsuya Nagae, et al.
    • Journal Title

      Kidney International 74

      Pages: 70-80

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Atrial natriuretic peptide prevents peritoneal adhesion formation with inhibiting macrophage and CD3-positive cell infiltration.2010

    • Author(s)
      Yokoi H, Kasahara M, Mori K, Kuwabara T, Imamaki H, Kawanishi T, Koga K, Ishii A, Mori K, Kato Y, Sugawara A, Mukoyama M, Nakao K
    • Organizer
      第43回米国腎臓学会学術集会
    • Place of Presentation
      デンバー、アメリカ
    • Year and Date
      2010-11-18
    • Related Report
      2010 Final Research Report
  • [Presentation] Renoprotective role of natriuretic peptide family in various nephropathy models and its potential to clinical application.2010

    • Author(s)
      Mukoyama M, Mori K, Kasahara M, Yokoi H, Ogawa Y, Kuwabara T, Nakao K
    • Organizer
      第12回アジア太平洋腎臓学会
    • Place of Presentation
      ソウル、韓国
    • Year and Date
      2010-06-07
    • Related Report
      2010 Final Research Report
  • [Presentation] Renoprotective role of natriuretic peptide familiy in various nephropathy model and its potential to clinical application.2010

    • Author(s)
      Masashi Mukoyama
    • Organizer
      12th Asian-Pacific Congers of Nephrology
    • Place of Presentation
      ソウル国際会議場(ソウル市)韓国
    • Year and Date
      2010-06-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] Natriuretic peptide receptor guanylyl cyclase-A signaling exerts antagonistic effects on the local renin-angiotensin- aldosterone system in kidney.2010

    • Author(s)
      Ogawa Y, Mukoyama M, Yokoi H, Kasahara M, Mori K, Yoshioka T, Saito Y, Kuwabara T, Imamaki H, Kawanishi T, Koga K, Ishii A, Kishimoto I, Sugawara A, Nakao K
    • Organizer
      国際腎臓学会Nexus Symposium 2010
    • Place of Presentation
      京都
    • Year and Date
      2010-04-16
    • Related Report
      2010 Final Research Report
  • [Presentation] Role of cardiovascular hormones in renal disease.2010

    • Author(s)
      Mukoyama M, Mori K, Kasahara M, Yokoi H, Nakao K
    • Organizer
      第14回国際内分泌学会(シンポジウム)
    • Place of Presentation
      京都
    • Year and Date
      2010-03-29
    • Related Report
      2010 Final Research Report
  • [Presentation] Role of cardiovascular hormones in renal disease.2010

    • Author(s)
      Masashi Mukoyama
    • Organizer
      14th International Congress of Endocrinology
    • Place of Presentation
      国立京都国際会館(京都市)
    • Year and Date
      2010-03-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] Protective effects of natriuretic peptide receptor guanylyl cyclase-A signaling on aldosteroneinduced glomerular injury.2009

    • Author(s)
      Mukoyama M, Ogawa Y, Yokoi H, Kasahara M, Mori K, Yoshioka T, Saito Y, Kuwabara T, Imamaki H, Kishimoto I, Sugawara A, Nakao K
    • Organizer
      2009年世界腎臓学会
    • Place of Presentation
      ミラノ、イタリア
    • Year and Date
      2009-05-25
    • Related Report
      2010 Final Research Report
  • [Presentation] Protective effect of atrial natriuretic peptide receptor guanylyl cyclase-A signaling on aldosteroneinduced renal injury.2008

    • Author(s)
      Ogawa Y, Mukoyama M, Yokoi H, Kasahara M, Mori K, Yoshioka T, Saito Y, Kuwabara T, Imamaki H, Sugawara A, Nakao K
    • Organizer
      第41回米国腎臓学会学術集会
    • Place of Presentation
      フィラデルフィア、アメリカ
    • Year and Date
      2008-11-06
    • Related Report
      2010 Final Research Report
  • [Presentation] Protective effect of atrial natriuretic peptide receptor guanylyl cyclase-A signaling on aldosterone-induced renal injury.2008

    • Author(s)
      Yoshihisa Ogawa, et al.
    • Organizer
      41st Annual Meeting of the American Society of Nephrology
    • Place of Presentation
      米国フィラデルフィア
    • Year and Date
      2008-11-06
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://www.kuhp.kyoto-u.ac.jp/~med2/index-jp.html

    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] 腹膜癒着防止用医薬組成物2010

    • Inventor(s)
      中尾一和、横井秀基、向山政志、笠原正登、森潔、古谷真優美
    • Industrial Property Rights Holder
      国立大学法人京都大学、第一三共株式会社
    • Industrial Property Number
      2010-051171
    • Filing Date
      2010-03-08
    • Related Report
      2010 Final Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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