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Investigation of renal fibrosis molecular mechanisms focusing on membrane proteins

Research Project

Project/Area Number 18K08233
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53040:Nephrology-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

YUI Naofumi  東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (00633976)

Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords腎臓線維化 / 細胞骨格 / ミオシン / アクチン / 細胞膜輸送体 / 慢性腎臓病 / 非筋肉型ミオシン / レンチウイルス / ノックダウン / 線維芽細胞 / 筋線維芽細胞 / α平滑筋アクチン
Outline of Final Research Achievements

In this study, We investigated what kind of molecules are accumulated in plasma membrane of renal fibroblasts during its differentiation into myofibroblast. We performed cell surface biotinylation assays with or without TGF-b1 stimulation using NRK-49F rat renal fibroblast. The collected molecules are analyzed using silver-staining and LC-MS. We identified MYH-9 as a membrane protein of renal fibroblast during its differentiation. Using its specific inhibitor, blebbistatin, and lentivirus-mediated gene knockdown, its importance on aSMA production, Smad2/3 nucleus transportation are clearly demonstrated. Upon differentiation into myofibroblast, MYH-9 accumulated in plasma membrane and nucleus. By inhibition using blebbistation, MYH-9 accumulation on plasma membrane and nucleus was blocked, and TGF-b1 induced aSMA production, Smad2/3 nuclear acccumulation were suppressed.

Academic Significance and Societal Importance of the Research Achievements

本邦では慢性腎臓病は8人に1人が罹患しているとされ国民的疾患概念である。この進行を緩やかにし腎不全の発症を抑制することは今後の医療の最も重要な課題の一つと言える。そのためには原因疾患は何であれ共通する病態生理である腎臓線維化を治療できるようにすることが必要となる。腎臓線維化がどのような機序で進展してゆくのかを解明することが重要な一歩になる。今回腎臓の線維芽細胞が活性化する際にどのような分子が細胞膜を貫通する形で集積するかを分子生物学的手法を用いて研究しMYH-9という分子を同定し機能を解析しその重要性を細胞生物学的に示すことが出来た。今後のこの領域の研究の方向性に貢献しうるものと考える。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (8 results)

All 2022 2020 2019 2018

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (5 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] LRBA is essential for urinary concentration and body water homeostasis2022

    • Author(s)
      Hara Y, Ando F, Oikawa D, Ichimura K, Yanagawa H, Sakamaki Y, Nanamatsu A, Fujiki T, Mori S, Suzuki S, Yui N, Mandai S, Susa K, Mori T, Sohara E, Rai T, Takahashi M, Sasaki S, Kagechika H, Tokunaga F, Uchida S.
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 119 Issue: 30

    • DOI

      10.1073/pnas.2202125119

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chlorpromazine Induces Basolateral Aquaporin-2 Accumulation via F-Actin Depolymerization and Blockade of Endocytosis in Renal Epithelial Cells.2020

    • Author(s)
      Yui N, Bouley R, Terlouw A, Cheung PW, Brown D.
    • Journal Title

      Cells

      Volume: 23 Issue: 4 Pages: 1057-1057

    • DOI

      10.3390/cells9041057

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] AKAPs-PKA disruptors increase AQP2 activity independently of vasopressin in a model of nephrogenic diabetes insipidus2018

    • Author(s)
      Ando Fumiaki、Mori Shuichi、Yui Naofumi、Morimoto Tetsuji、Nomura Naohiro、Sohara Eisei、Rai Tatemitsu、Sasaki Sei、Kondo Yoshiaki、Kagechika Hiroyuki、Uchida Shinichi
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 1411-1411

    • DOI

      10.1038/s41467-018-03771-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 腎臓線維芽細胞活性化における非筋肉型ミオシン 2A の重要性2020

    • Author(s)
      油井 直史,名和 眞希子,内田 信一.
    • Organizer
      日本腎臓学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Derivatives of FMP-API-1/27 Robustly Activate AQP2 Water Channels Independently of Vasopressin2019

    • Author(s)
      Ando, Fumiaki, Yui, Naofumi, Mandai, Shintaro, Isobe, Kiyoshi, Mori, Takayasu, Susa, Koichiro, Nomura, Naohiro, Sohara, Eisei, Rai, Tatemitsu, Uchida, Shinichi,
    • Organizer
      American Society of Nephrology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Epithelial Depolarization Induces AQP2 Up-regulation via Non-Canonical Ser-269 Phospho-Regulation Independently of Any Hormonal and Chemical Stimulation2018

    • Author(s)
      Yui Naofumi、Ando Fumiaki、Sasaki Sei、Uchida Shinichi
    • Organizer
      American Society of Nephrology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] AKAPs-PKA Disruptors Robustly Increase AQP2 Activity Independently of Vasopressin2018

    • Author(s)
      Ando Fumiaki、Yui Naofumi、Nomura Naohiro、Rai Tatemitsu、Sasaki Sei、Uchida Shinichi
    • Organizer
      American Society of Nephrology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Phosphorylation of Ser261 and Dephosphorylation of Ser269 Is Important for Urinary Excretion of AQP22018

    • Author(s)
      Sasaki Sei、Sakai Masaki、Mizumura Hiroki、Matsumoto Tomoki、Noda Yumi、Yui Naofumi、Ishibashi Kenichi
    • Organizer
      American Society of Nephrology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2024-01-30  

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