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Elucidation of the role of Rac1 and MR in obese diabetic nephropathy and attempt at a novel therapeutic agent

Research Project

Project/Area Number 22790782
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Kidney internal medicine
Research InstitutionThe University of Tokyo

Principal Investigator

YOSHIDA Shigetaka  東京大学, 医学部・附属病院, 特任助教 (30559430)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords慢性腎疾患 / 高血圧 / 糖尿病 / アルドステロン
Research Abstract

We showed renal Rac1 and MR activation in obese diabetic mice, and oral administration of low dose MR blockade and Rac1 inhibitor respectively ameliorated nephropathy. Experiment of cultured renal cells revealed that glucose aldosterone-independently activates MR via Rac1 activation, and suppression of Rac1 activity diminished MR activation by glucose stimulation. These result showed the important role of Rac1/MR axis in obese diabetic kidney, and suggests the possible efficacy of Rac1 suppression in the treatment strategy of diabetic nephropathy, of which incidence and progression have not been sufficiently prevented despite striking progression of antihypertensive and antidiabetic therapy.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (7 results)

All 2011 2010

All Presentation (7 results)

  • [Presentation] 腎糸球体メサンギウム細胞における高血糖による低分子G蛋白Rac1の活性化とミネラルコルチコイド受容体活性化2011

    • Author(s)
      吉田成孝
    • Organizer
      第15回日本心血管内分泌代謝学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2011-11-26
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Local, ligand-independent mineralocorticoid receptor activation by high glucose stimulation via Rac12010

    • Author(s)
      Shigetaka YOSHIDA
    • Organizer
      The 23rd Scientific Meeting of the International Society of Hypertension
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2010-09-28
    • Related Report
      2011 Final Research Report
  • [Presentation] Local, ligand-independent mineralocorticoid receptor activation by high glucose stimulation via Rac1.2010

    • Author(s)
      吉田成孝
    • Organizer
      The 23rd Scientific Meeting of the International Society of Hypertension
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2010-09-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] Local, ligand-independent mineralocorticoid receptor activation by high glucose stimulation via Rac12010

    • Author(s)
      Shigetaka YOSHIDA
    • Organizer
      36th Annual Meeting of the International Aldosterone Conference
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2010-06-18
    • Related Report
      2011 Final Research Report
  • [Presentation] Local, ligand-independent mineralocorticoid receptor activation by high glucose stimulation via Rac1.2010

    • Author(s)
      吉田成孝
    • Organizer
      36th Annual Meeting of the International Aldosterone Conference
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2010-06-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] Local, ligand-independent mineralocorticoid receptor activation by high glucose stimulation via Rac12010

    • Author(s)
      Shigetaka YOSHIDA
    • Organizer
      International Society of Nephrology NEXUS Symposium 2010
    • Place of Presentation
      京都
    • Year and Date
      2010-04-16
    • Related Report
      2011 Final Research Report
  • [Presentation] Local, ligand-independent mineralocorticoid receptor activation by high glucose stimulation via Rac1.2010

    • Author(s)
      吉田成孝
    • Organizer
      International Society of Nephrology NEXUS Symposium 2010
    • Place of Presentation
      京都
    • Year and Date
      2010-04-16
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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