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An examination of whether the autophagy in the renal tubule cell could be a new therapeutic target of chronic kidney disease.

Research Project

Project/Area Number 22590889
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionShiga University of Medical Science

Principal Investigator

UZU Takashi  滋賀医科大学, 医学部, 准教授 (20422884)

Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords慢性腎臓病 / オートファジー / 近位尿細管 / AtG5 / 蛋白尿 / 肥満腎症 / 尿細管 / 加齢腎症
Research Abstract

Autophagy is an intracellular degradation system to protect cells by removing damaged proteins and organelles. We examined the role of autophagy in obesity-mediated exacerbation of proteinuria-induced tubular damages. In non-obese mice, proteinuria induced by intraperitoneal albumin-overload led to mild proximal tubular epithelial cell damage and apoptosis. In contrast, high fat diet-induced obesity suppressed proteinuria-induced autophagy in proximal tubular cells and exacerbated proteinuria-induced proximal cell damage and apoptosis. Proximal tubular cell -specific autophagy-deficient mice developed severe proteinuria-induced proximal tubular cell damage, suggesting that proteinuria-induced autophagy was renoprotectively elicited. Autophagy insufficiency was ameliorated by treatment with the mammalian target of rapamycin (mTOR) inhibitor. These results suggest that a restoration of the renoprotective action of autophagy in proximal tubular epithelial cells become a new therapeutic approach to improve the renal outcome.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (13 results)

All 2012 2011 2010 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (7 results)

  • [Journal Article] a novel therapeutic target for kidney diseases2012

    • Author(s)
      Kume S, Uzu T, Maegawa H, Koya D. Autophagy
    • Journal Title

      Clin Exp Nephrol.

      Volume: 16:827-32

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Autophagy as a therapeutic target in diabetic nephropathy2012

    • Author(s)
      Tanaka Y, Kume S, Kitada M, Kanasaki K, Uzu T, Maegawa H, Koya D
    • Journal Title

      Exp Diabetes Res.

      Volume: 628978

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Autophagy as a therapeutic target in diabetic nephropathy2012

    • Author(s)
      Tanaka Y, Kume S, Kitada M, Kanasaki K, Uzu T, Maegawa H, Koya D
    • Journal Title

      Exp Diabetes Res

      Volume: 2012 Pages: 1-12

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SIRT3 attenuates palmitate-induced ROS production and inflammation in proximal tubular cells2011

    • Author(s)
      Koyama T, Kume S, Uzu T 他
    • Journal Title

      Free Radic Biol Med

      Volume: 51:1258-67

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] SIRT3 attenuates palmitate-induced ROS production and inflammation in proximal tubular cells2011

    • Author(s)
      Koyama T, Kume S, Koya D, Araki S, Isshiki K, Kanasaki CM, Sugimoto T, Haneda M, Sugaya T, Kashiwagi A, Maegawa H, Uzu T
    • Journal Title

      Free Radic Biol Med

      Volume: 51 Pages: 1258-1267

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Obesity-mediated autophagy insufficiency exacerbates proteinuria induced tubulointerstitial lesions.

    • Author(s)
      Yamahara K, Kume S, Uzu T 他
    • Journal Title

      J Am Soc Nephrol in press

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Presentation] 高脂肪食負荷肥満マウスの腎尿細管病変進展におけるオートファジーの役割2012

    • Author(s)
      山原康佑、宇津 貴
    • Organizer
      日本糖尿病性腎症研究会
    • Place of Presentation
      東京
    • Year and Date
      2012-12-01
    • Related Report
      2012 Final Research Report
  • [Presentation] 肥満や加齢に伴う尿蛋白誘導性尿細管障害の悪化における小胞体ストレスの関与2012

    • Author(s)
      武田尚子、宇津 貴
    • Organizer
      日本腎臓学会学術総会
    • Place of Presentation
      横浜市
    • Year and Date
      2012-06-01
    • Related Report
      2012 Final Research Report
  • [Presentation] 慢性腎臓病とオートファジー2011

    • Author(s)
      久米真司、宇津 貴
    • Organizer
      日本腎臓学会西武学術大会
    • Place of Presentation
      徳島市
    • Year and Date
      2011-09-30
    • Related Report
      2012 Final Research Report
  • [Presentation] Uuz T Autophagy deficiency in obese and aging mice exacerbates proteinuria-related renal tbulointerstitial lesion2011

    • Author(s)
      Kume S
    • Organizer
      71st meeting of American Diabetes Association
    • Place of Presentation
      サンディエゴ市
    • Year and Date
      2011-06-28
    • Related Report
      2012 Final Research Report
  • [Presentation] 尿蛋白に伴う腎尿細管間質病変進展における近位尿細管細胞オートファジーの役割2011

    • Author(s)
      久米真司, 古家大祐, 荒木信一, 一色啓二, 羽田勝計, 前川聡, 宇津貴
    • Organizer
      日本腎臓学会
    • Place of Presentation
      横浜市
    • Year and Date
      2011-06-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] 糖尿病腎症治療における抗老化分子Sirt1の可能性2010

    • Author(s)
      久米真司
    • Organizer
      第53回日本腎臓学会学術総会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2010-06-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] 高脂肪食負荷肥満マウスの腎尿細管病変進展におけるオートファジーの役割

    • Author(s)
      山原康佑
    • Organizer
      日本糖尿病学会
    • Place of Presentation
      熊本市
    • Related Report
      2012 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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