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Strategies aimed at modulating autophagy for treating kidney diseases

Research Project

Project/Area Number 15H06371
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Kidney internal medicine
Research InstitutionOsaka University

Principal Investigator

Yamamoto Takeshi  大阪大学, 医学部附属病院, 医員 (20756994)

Project Period (FY) 2015-08-28 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsオートファジー / フラックス / 近位尿細管 / 老化 / Rubicon / クロロキン / 尿細管 / エベロリムス
Outline of Final Research Achievements

Autophagy plays an essential role for cellular homeostasis. Here, we established the methods for monitoring autophagic flux in vivo by using GFP-LC3 transgenic mice and tamoxifen-inducible proximal tubule-specific autophagy-deficient mice. Using the methods, we investigated the impact of altered autophagic flux in kidney aging. Furthermore, we newly established mice models in which autophagic flux is genetically (Rubicon, a Beclin1-interacting negative regulator for autophagosome-lysosome fusion, knockout mice) and pharmacologically(omega-3 fatty acid, EPA) enhanced. Proximal tubule-specific Rubicon knockout mice showed high autophagic flux in basal and stressed conditions and exhibited significant improvement of kidney injury in some choronic kidey disease models. Also, EPA attenuated renal lipotoxicity by improving autophagic flux in obese mice kidneys. Modulating autophagic flux would be a potentially important therapeutic target for regulating progression of kidney diseases.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • Research Products

    (4 results)

All 2016 2015

All Journal Article (2 results) (of which Peer Reviewed: 1 results,  Acknowledgement Compliant: 1 results) Presentation (2 results)

  • [Journal Article] Time-dependent dysregulation of autophagy: Implications in aging and mitochondrial homeostasis in the kidney proximal tubule.2016

    • Author(s)
      Yamamoto T, Takabatake Y, Kimura T, Takahashi A, Namba T, Matsuda J, Minami S, Kaimori JY, Matsui I, Kitamura H, Matsusaka T, Niimura F, Yanagita M, Isaka Y, Rakugi H.
    • Journal Title

      Autophagy

      Volume: 12 Issue: 5 Pages: 801-13

    • DOI

      10.1080/15548627.2016.1159376

    • NAID

      40021034920

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 加齢によるオートファジー活性の変化がミトコンドリア機能低下を介して腎老化を引き起こす2016

    • Author(s)
      山本毅士
    • Journal Title

      日本腎臓学会誌

      Volume: 58 Pages: 1238-1242

    • Related Report
      2016 Annual Research Report
  • [Presentation] Time-dependent dysregulation of autophagy: Implications in aging and mitochondrial homeostasis in the kidney proximal tubule2016

    • Author(s)
      山本毅士
    • Organizer
      第38回腎臓セミナー・Nexus Japan
    • Place of Presentation
      東京
    • Year and Date
      2016-08-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] 加齢によるオートファジー活性の変化がミトコンドリア機能低下を介して腎老化を引き起こす2015

    • Author(s)
      山本毅士
    • Organizer
      第6回分子腎臓フォーラム
    • Place of Presentation
      大阪
    • Year and Date
      2015-09-05
    • Related Report
      2015 Annual Research Report

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Published: 2015-08-26   Modified: 2018-03-22  

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