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Effect of V-ATPase inhibition in renal fibrosis

Research Project

Project/Area Number 17K16092
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Kidney internal medicine
Research InstitutionTohoku Medical and Pharmaceutical University

Principal Investigator

Yabana Ikuko  東北医科薬科大学, 医学部, 助教 (60778596)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords腎臓 / 線維化 / 細胞内タンパク質輸送 / 酸性オルガネラ / V-ATPase / 細胞内蛋白輸送 / 腎線維化 / 慢性腎臓病
Outline of Final Research Achievements

The vacuolar ATPase (V-ATPase) regulates the pH of organelle vesicles and is involved in the intracellular and extracellular transport of proteins. We investigated the effect of V-ATPase inhibition on fibrosis in the kidney. First, we examined the effect of bafilomycin (BAF: V-ATPase inhibitor) on TGF-β-induced fibrosis in M1 cells derived from mouse renal cortical collecting ducts. The fibrotic proteins induced by TGF-β were trapped in the cytoplasmic organelle by V-ATPase inhibition. Next, we investigated the effect of BAF on renal fibrosis in a renal fibrosis model, UUO. Fibrosis induced by the UUO was partially inhibited in the BAF-treated group compared to the control group. However, the increase in liver weight and hepatic fibrosis were observed, meaning the hepatotoxicity was stronger than the inhibitory effect of BAF on fibrosis.

Academic Significance and Societal Importance of the Research Achievements

腎線維化の進展にはV-ATPaseにより調節される細胞内酸性オルガネラを介したタンパク質輸送が関与している。障害により誘導された線維化タンパク質は、V-ATPase阻害により細胞外への輸送が抑制され、細胞内の酸性オルガネラにとどまるようになる。組織障害に伴う線維化に対し、障害を受けた組織特異的なV-ATPase阻害により線維化を抑制し、組織を保護できる可能性が示唆された。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (14 results)

All 2020 2019 2018 2017 Other

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

  • [Journal Article] Acidic organelles mediate TGF-β1-induced cellular fibrosis via (pro)renin receptor and vacuolar ATPase trafficking in human peritoneal mesothelial cells.2018

    • Author(s)
      1: Oba-Yabana I, Mori T, Takahashi C, Hirose T, Ohsaki Y, Kinugasa S, Muroya Y, Sato E, Nguyen G, Piedagnel R, Ronco PM, Totsune K, Ito S
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 2648-2648

    • DOI

      10.1038/s41598-018-20940-x

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 腎うっ血における腎循環とバゾプレシン2型受容体の役割の検討.2020

    • Author(s)
      森建文, 廣瀬卓男, 大崎雄介, 髙橋知香, 矢花郁子.
    • Organizer
      第30回バゾプレシン研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Exon 4-encoded domain of (pro)renin receptor impairs several V-ATPase-mediated functions.2019

    • Author(s)
      Hirose T, Cabrera-Socorro A, Matsuki T, Takahashi C, Oba-Yabana I, Kinugasa S, Muroya Y, Tani J, Nguyen G, Groszer M, Ito S, Mori T.
    • Organizer
      ISARSH2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Low-vacuum scanning electron microscopy analysis for formalin-fixed paraffin-embedded rat kidney sections.2019

    • Author(s)
      Moriyama S, Takeuchi W, Kaburaki T, Shimada K, Hirose T, Kinugasa S, Matsuki T, Oba-Yabana I, Muroya Y, Mori T.
    • Organizer
      World Congress of Nephrology 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 腎集合管細胞に対する筋由来生理活性物質アイリシンの効果の検討.2019

    • Author(s)
      廣瀬卓男, 髙橋知香, 矢花郁子, 加藤季子, 関敬之, 中村はな, 衣笠哲史, 谷淳一, 森建文.
    • Organizer
      第23回日本心血管内分泌代謝学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 光学顕微鏡用腎組織標本の低真空走査電子顕微鏡を用いた観察.2019

    • Author(s)
      廣瀬卓男, 髙橋知香, 松木琢磨, 中山晋吾, 衣笠哲史, 矢花郁子, 加藤季子, 関敬之, 中村はな, 谷淳一, 森建文.
    • Organizer
      第48回宮城県腎不全研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 腹膜中皮細胞における(プロ)レニン受容体の役割の検討2018

    • Author(s)
      廣瀬卓男 矢花郁子 高橋知香 衣笠哲史 室谷嘉一 伊藤貞嘉 森建文
    • Organizer
      日本透析医学会
    • Related Report
      2018 Research-status Report
  • [Presentation] ポドサイト障害に対するVATPaseの評価2018

    • Author(s)
      松木琢磨 森建文 高橋知香 矢花郁子 大崎雄介 廣瀬卓男 熊谷直憲 伊藤貞嘉
    • Organizer
      日本腎臓学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 腹膜透析におけるV-ATPaseと(pro)renin受容体の役割2018

    • Author(s)
      森 建文、矢花郁子、廣瀬卓男、高橋知香、大崎雄介、佐藤 恵美子、伊藤貞嘉
    • Organizer
      第10回(プロ)レニン受容体フォーラム
    • Related Report
      2017 Research-status Report
  • [Presentation] 細胞内蛋白輸送による腹膜線維化機序2017

    • Author(s)
      森 建文、矢花郁子
    • Organizer
      第23回日本腹膜透析医学会学術集会・総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 酸性オルガネラによる蛋白輸送は腹膜透析におけるグルコース分解産物(GDPs)誘導性腹膜線維化に関与する2017

    • Author(s)
      矢花郁子、大崎雄介、高橋知香、伊藤貞嘉、森 建文
    • Organizer
      第60回日本腎臓学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 腎線維化における集合管酸性オルガネラの役割2017

    • Author(s)
      森 建文、高橋知香、矢花郁子、大崎雄介、衣笠哲史、伊藤貞嘉
    • Organizer
      第60回日本腎臓学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 培養ポドサイト線維化機序に対するV-ATPaseの評価2017

    • Author(s)
      松木琢磨、森 建文、高橋知香、矢花郁子、大崎雄介、熊谷直憲、伊藤貞嘉
    • Organizer
      第60回日本腎臓学会学術総会
    • Related Report
      2017 Research-status Report
  • [Remarks] 東北医科薬科大学 内科学第三(腎臓内分泌内科)教室

    • URL

      https://tohokupd.jimdo.com

    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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