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Structure-function association in podocytopathy via Rho family small G proteins

Research Project

Project/Area Number 26670427
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Kidney internal medicine
Research InstitutionJuntendo University

Principal Investigator

Nagase Miki  順天堂大学, 医学(系)研究科(研究院), 准教授 (60302733)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsポドサイト傷害 / Rac1 / アクチン細胞骨格 / 細胞の運動性 / 低分子量G蛋白質 / 鉱質コルチコイド受容体 / マクロファージ / 心筋細胞 / Rac1 / ポドサイト障害 / オプトジェネティクス / 細胞骨格 / アクチン
Outline of Final Research Achievements

Rac1, a Rho family small GTPase, is a multi-functional molecule that controls cytoskeleton, oxidative stress, gene transcription, and cell motility, in a cell-specific manner. In this study, we analyzed the role of Rac1 in the pathobiology of glomerular podocytes, focusing on the structure-function association, and compared its roles in other cells. In podocytes, both Rac1 hyperactivation and hypoactivation resulted in podocyte injury, albuminuria, and glomerulosclerosis, and affected actin cytoskeleton and cell motility by distinct mechanisms. Macrophage Rac1 played a central role in lipopolysaccharide-evoked acute kidney injury through M1 cytokine production. Cardiomyocyte Rac1 contributed to the pressure overload-induced heart failure via induction of NOX4.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (17 results)

All 2016 2015 2014 Other

All Int'l Joint Research (1 results) Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 1 results,  Acknowledgement Compliant: 3 results) Presentation (12 results) (of which Int'l Joint Research: 2 results,  Invited: 9 results) Remarks (1 results)

  • [Int'l Joint Research] Hudson Institute of Medical Research(Australia)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Deletion of Rac1GTPase in the Myeloid Lineage Protects against Inflammation-Mediated Kidney Injury in Mice2016

    • Author(s)
      Nagase M, Kurihara H, Aiba A, Young MJ, Sakai T
    • Journal Title

      PLoS One

      Volume: 11 Issue: 3 Pages: e0150886-e0150886

    • DOI

      10.1371/journal.pone.0150886

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Rac1-Mediated Activation of Mineralocorticoid Receptor in Pressure Overload-Induced Cardiac Injury2016

    • Author(s)
      Nobuhiro Ayuzawa, Miki Nagase, Kohei Ueda, Mitsuhiro Nishimoto, Wakako Kawarazaki, Takeshi Marumo, Atsu Aiba, Takayuki Sakurai, Takayuki Shindo, Toshiro Fujita
    • Journal Title

      Hypertension

      Volume: 67 Issue: 1 Pages: 99-106

    • DOI

      10.1161/hypertensionaha.115.06054

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Recent topics on podocytes and aldosterone2015

    • Author(s)
      Miki Nagase
    • Journal Title

      J Ren Nutr

      Volume: 25 Issue: 2 Pages: 201-204

    • DOI

      10.1053/j.jrn.2014.10.016

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Expression and Localization of Mineralocorticoid Receptor in the Non-Classical Target Organs of Aldosterone in Mice2016

    • Author(s)
      Kohei Ueno, Miki Nagase, Koki Yasunaga, Tatsuo Sakai
    • Organizer
      41st International Aldosterone Conference
    • Place of Presentation
      Boston, USA
    • Year and Date
      2016-03-30
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Roles of Mineralocorticoid and Glucocorticoid Receptors in the Hippocampal Lesion Formation in Mice2016

    • Author(s)
      Koki Yasunaga, Miki Nagase, Kohei Ueno, Tatsuo Sakai
    • Organizer
      41st International Aldosterone Conference
    • Place of Presentation
      Boston, USA
    • Year and Date
      2016-03-30
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 食塩と高血圧2015

    • Author(s)
      長瀬美樹
    • Organizer
      第38回日本高血圧学会総会
    • Place of Presentation
      愛媛
    • Year and Date
      2015-10-11
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 長瀬美樹、坂井建雄. 鉱質コルチコイド受容体と腎脂肪連関2015

    • Author(s)
      長瀬美樹、坂井建雄
    • Organizer
      第38回日本高血圧学会総会
    • Place of Presentation
      愛媛
    • Year and Date
      2015-10-09
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 生活習慣病に伴う腎障害とジェネティック・エピジェネティック制御2015

    • Author(s)
      長瀬美樹、坂井建雄
    • Organizer
      第52回日本臨床分子医学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2015-04-11
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Regulation of podocyte structure and function: roles of Rho family proteins and their modulators2015

    • Author(s)
      Miki Nagase, Tatsuo Sakai
    • Organizer
      The Joint Meeting of the 120th Annual Meeting of the Japanese Association of Anatomists the 92nd Annual Meeting of the Physiological Society of Japan (Symposium)
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-21
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 鉱質コルチコイド受容体と腎障害2015

    • Author(s)
      長瀬美樹
    • Organizer
      中原CKDラウンドテーブルディスカッション
    • Place of Presentation
      川崎
    • Year and Date
      2015-02-05
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Rac1-mineralocorticoid receptor pathway in rodent macrophage contributes to inflammation-mediated kidney injury (oral)2014

    • Author(s)
      Miki Nagase, Tatsuo Sakai
    • Organizer
      Cold Spring Harbor Laboratory Meetings & Courses 2014 Nuclear receptors and disease
    • Place of Presentation
      New York, USA
    • Year and Date
      2014-11-01
    • Related Report
      2014 Research-status Report
  • [Presentation] 鉱質コルチコイド受容体研究の新展開とアルドステロンブロッカーの新たな可能性2014

    • Author(s)
      長瀬美樹
    • Organizer
      第44回日本腎臓学会東部学術集会
    • Place of Presentation
      東京
    • Year and Date
      2014-10-24
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 鉱質コルチコイド受容体、糖質コルチコイド受容体と腎障害2014

    • Author(s)
      長瀬美樹
    • Organizer
      第5回メタボリックシンドロームと血管研究会
    • Place of Presentation
      東京
    • Year and Date
      2014-10-11
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Role of Rac1 in podocyte injury and glomerulosclerosis2014

    • Author(s)
      Miki Nagase, Tatsuo Sakai, Toshiro Fujita
    • Organizer
      International Society of Nephrology Nexus symposium
    • Place of Presentation
      Brisbane, Australia
    • Year and Date
      2014-09-24
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 鉱質コルチコイド受容体(MR)と食塩感受性高血圧2014

    • Author(s)
      長瀬美樹
    • Organizer
      第57回日本腎臓学会学術総会 シンポジウム
    • Place of Presentation
      横浜
    • Year and Date
      2014-07-05
    • Related Report
      2014 Research-status Report
    • Invited
  • [Remarks] 順天堂大学大学院 解剖学・生体構造科学

    • URL

      http://www.juntendo.ac.jp/graduate/laboratory/labo/kaibou_seitaikouzo/k4.html

    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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