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Examination of inhibition effect by monosaccharide analog for renal cyst progression in polycystic kidney disease

Research Project

Project/Area Number 18K08257
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53040:Nephrology-related
Research InstitutionFujita Health University

Principal Investigator

Nakajima Kazuki  藤田医科大学, 共同利用研究設備サポートセンター, 講師 (10442998)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords嚢胞性腎疾患群 / 糖脂質 / グルコース代謝 / 糖ヌクレオチド / グライコミクス / メタボロミクス / 細胞増殖 / 嚢胞性腎疾患 / 糖鎖修飾 / グルコシルセラミド / O-GlcNAc化 / マンノース代謝 / 多発性嚢胞腎 / グルコース化脂質 / O-GlcNAc
Outline of Final Research Achievements

Polycystic kidney disease is characterized by the progressive development of kidney and liver cysts. In this study, I elucidated how treatment with a modified sugar analog disrupts a biological pathway, which in turn block cyst progression.
6-alkynyl fucose was thought to block liver cyst progression via glycan changes, in contrast, 6-azido xylose blocked cell progression in renal cyst-derived cell lines. As other targets, 2-deoxyglucose and Venglustat, inhibitors of glucose metabolism and glycosphingolipid synthesis, cooperatively blocked the cell progression in the cyst-derived cells. Moreover, I identified novel monosaccharide-activated nucleotide sugars (GDP-2-deoxy-mannose and UDP-mannose) as key regulators in glycosylation. Therefore, our hypothesis will provide novel therapeutic targets and valuable insights regarding the molecular mechanisms in polycystic kidney diseases.

Academic Significance and Societal Importance of the Research Achievements

嚢胞性腎疾患群に対する薬物治療法は、唯一トルバプタンのみであり新たな治療方法の確立が望まれている。今回の研究で検討した単糖代謝阻害剤は、その阻害剤の効果を高めることで新たなシード化合物になりえる。また、その阻害剤と別経路の糖脂質代謝阻害剤さらにトルバプタンの併用は、実臨床に近い薬剤を組み合わせた新たな併用療法につながると考えている。さらに今回の研究で検出された希少糖ヌクレオチドは、糖鎖修飾の新たな制御因子になりうることから、嚢胞腎研究や生化学研究において新たな発展が期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (18 results)

All 2021 2020 2019 2018

All Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 9 results,  Open Access: 6 results) Presentation (7 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Book (1 results)

  • [Journal Article] Protocol for analyzing the biosynthesis and degradation of N-glycan precursors in mammalian cells2021

    • Author(s)
      Harada Y, Nakajima K, Li S, Suzuki T, Taniguchi N.
    • Journal Title

      STAR Protoc.

      Volume: 2 Issue: 1 Pages: 100316-100316

    • DOI

      10.1016/j.xpro.2021.100316

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rab11-mediated post-Golgi transport of the sialyltransferase ST3GAL4 suggests a new mechanism for regulating glycosylation2021

    • Author(s)
      Kitano Masato、Kizuka Yasuhiko、Sobajima Tomoaki、Nakano Miyako、Nakajima Kazuki、Misaki Ryo、Itoyama Saki、Harada Yoichiro、Harada Akihiro、Miyoshi Eiji、Taniguchi Naoyuki
    • Journal Title

      Journal of Biological Chemistry

      Volume: 296 Pages: 100354-100354

    • DOI

      10.1016/j.jbc.2021.100354

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glycometabolic Regulation of the Biogenesis of Small Extracellular Vesicles2020

    • Author(s)
      Harada Yoichiro、Nakajima Kazuki、Suzuki Takehiro、Fukushige Tomoko、Kondo Kiyotaka、Seino Junichi、Ohkawa Yuki、Suzuki Tadashi、Inoue Hiromasa、Kanekura Takuro、Dohmae Naoshi、Taniguchi Naoyuki、Maruyama Ikuro
    • Journal Title

      Cell Reports

      Volume: 33 Issue: 2 Pages: 108261-108261

    • DOI

      10.1016/j.celrep.2020.108261

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mass spectrometry for the identification and analysis of highly complex glycosylation of therapeutic or pathogenic proteins2020

    • Author(s)
      Ohyama.Y, Nakajima.K, Reinfow MB, Novak J. Takahashi K
    • Journal Title

      Expert Review of Proteomics

      Volume: 5 Issue: 4 Pages: 0-0

    • DOI

      10.1080/14789450.2020.1769479

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Neuroprotection by Neurotropin through Crosstalk of Neurotrophic and Innate Immune Receptors in PC12 Cells2020

    • Author(s)
      Fukuda Y, Nakajima K, Mutoh T.
    • Journal Title

      Int J Mol Sci .

      Volume: 21(18) Issue: 18 Pages: 6456-6456

    • DOI

      10.3390/ijms21186456

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analysis of O-glycoforms of the IgA1 hinge region by sequential deglycosylation.2020

    • Author(s)
      Ohyama Y, Yamaguchi H, Nakajima K, Mizuno T, Fukamachi Y, Yokoi Y, Tsuboi N, Inaguma D, Hasegawa M, Renfrow MB, Novak J, Yuzawa Y, Takahashi K.
    • Journal Title

      Sci Rep.

      Volume: 10(1) Issue: 1 Pages: 671-671

    • DOI

      10.1038/s41598-020-57510-z

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] UDP-グルコースを介するSNAI1 mRNAの分解調節はがん転移を抑制する2020

    • Author(s)
      中嶋和紀
    • Journal Title

      Farumashia

      Volume: 56 Issue: 4 Pages: 350-350

    • DOI

      10.14894/faruawpsj.56.4_350

    • NAID

      130007825106

    • ISSN
      0014-8601, 2189-7026
    • Related Report
      2019 Research-status Report
  • [Journal Article] Free Glycans Derived From O-mannosylated Glycoproteins Suggest the Presence of an O-glycoprotein Degradation Pathway in Yeast2019

    • Author(s)
      Hirayama H, Matsuda T, Tsuchiya Y, Oka R, Seino J , Huang C, Nakajima K , Noda Y, Shichino Y, Iwasaki S , Suzuki T
    • Journal Title

      J Biol Chem

      Volume: 294(44) Issue: 44 Pages: 15900-15900

    • DOI

      10.1074/jbc.ra119.009491

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bisecting GlcNAc Is a General Suppressor of Terminal Modification of N-glycan2019

    • Author(s)
      Nakano M, Mishra SK, Tokoro Y, Sato K, Nakajima K, Yamaguchi Y, Taniguchi N, Kizuka Y.
    • Journal Title

      Mol Cell Proteomics

      Volume: 18(10) Issue: 10 Pages: 2044-2057

    • DOI

      10.1074/mcp.ra119.001534

    • NAID

      120006731226

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mass spectrometry-based approach for development of biomarkers in IgA nephropathy: a pilot trial2018

    • Author(s)
      Kondo A, Takahashi K, Yamaguchi H, Yoshida Y, Mizuno T, Nakajima K, Hayashi H, Koide S, Inaguma D, Hasegawa M, Hiki Y, Yuzawa Y
    • Journal Title

      Fujita Medical Journal

      Volume: 4 Pages: 36-41

    • NAID

      130007381892

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Identification and characterization of UDP-mannose in human cell lines and mouse organs: Differential distribution across brain regions and organs2020

    • Author(s)
      Kazuki Nakajima
    • Organizer
      Glyco XXV, Milan, Italy,
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 健常人脳脊髄液に含まれるスフィンゴ糖脂質プロファイル2020

    • Author(s)
      中嶋和紀, 島さゆり、新美芳樹、植田晃広、武藤多津郎
    • Organizer
      スフィンゴテラピー研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] 健常人脳脊髄液に含まれるスフィンゴ糖脂質プロファイル2019

    • Author(s)
      中嶋和紀, 村手健一郎、島さゆり、水谷泰彰、新美芳樹、植田晃広、渡邉宏久、武藤多津郎
    • Organizer
      第40回 日本糖質学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] UDP-マンノースの検出と解析、組織分布について2018

    • Author(s)
      中嶋和紀、木塚康彦、山口芳樹、平林義雄、高橋和男、湯澤由紀、谷口直之
    • Organizer
      第37回日本糖質学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 糖ヌクレオチド代謝に着目したメタボローム解析技術の構築―腎疾患の代謝メカニズム解析への応用―2018

    • Author(s)
      中嶋和紀
    • Organizer
      第91回日本生化学大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] DKDの新規バイオマーカー開発2018

    • Author(s)
      中嶋和紀
    • Organizer
      第48回日本腎臓学会西部学術総会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Lipidomics and metabolomics reveal metabolic crosstalk between elevated glycosphingolipids and glucose metabolisms in polycystic kidney progression2018

    • Author(s)
      Kazuki Nakajima, Kazuo Takahashi, Masanori Kugita, Shizuko Nagao, and Yukio Yuzawa.
    • Organizer
      International Society of Nephrology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Book] 糖鎖生物学 コラム42020

    • Author(s)
      中嶋和紀
    • Total Pages
      3
    • Publisher
      名古屋出版
    • ISBN
      9784815809812
    • Related Report
      2019 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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