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Significance of rare nucleotide sugar in of cell proliferation of cystic kidney disease

Research Project

Project/Area Number 21K08266
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Nakajima Kazuki  岐阜大学, 糖鎖生命コア研究所, 准教授 (10442998)

Co-Investigator(Kenkyū-buntansha) 長尾 静子  藤田医科大学, 病態モデル先端医学研究センター, 教授 (20183527)
高橋 和男  藤田医科大学, 医学部, 教授 (90631391)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords嚢胞性腎疾患群 / 糖ヌクレオチド / グライコプロテオミクス / グルコース代謝 / 細胞増殖 / 糖鎖バイオマーカー / 糖鎖修飾 / グライコミクス / LCMS / 嚢胞性腎疾患
Outline of Research at the Start

本研究では、マンノースなどを含む単糖機能性食品に着目して、嚢胞性腎疾患群という遺伝性腎疾患に対する予防療法もしくは、既存薬剤のトルバプタンとの併用療法を提案することが目的である。特に、マンノースから代謝・生合成されるUDP-マンノースやGDP-2-デオキシマンノースという希少糖ヌクレオチドに着目して、糖鎖修飾を介する病態形成機序を明らかにすることで、糖鎖変化による病態抑制効果を解明する。

Outline of Final Research Achievements

The purpose of this study is to propose preventive therapy for PKD, focusing on monosaccharide functional foods such as mannose via glycosylation. First, we have developed a hydrophilic interaction chromatography-ESI-MS/MS method for discovering rare-nucleotide sugars. UDP-deoxy-mannose and GDP-deoxy-mannose were detected in melanoma cell line supplemented with 2-deoxy glucose, by predicting multi-reaction monitoring method. On the other hands, UDP-mannose was expected to involve alpha1-2-mannosylation in N-glycan biosynthesis, by glycomics of Lec15 cell line supplemented with mannose. We also found different profiles of CA9-19 epitopes in urinary glycoproteins during PKD progression, indicating that the possibility of glycoprotein biomarkers in early diagnosis of PKD.

Academic Significance and Societal Importance of the Research Achievements

本研究は癌の個別化治療において着目されているマンノース療法を嚢胞腎に適用することを目指している。その一環で、希少糖ヌクレオチドの分析法開発と生化学的な意義解明、および糖鎖バイオマーカー開発を行ってきた。その効果は、糖鎖に基づいたPKDに対する予防療法や、治療の予後予測マーカーの確立につながる。本研究では、PKDにおけるUDP-マンノースやGDP-デオキシマンノースの意義を明らかにできなかったが、一方で発見された尿中の糖鎖変化は、キャリアータンパク質を同定することにより、癌と嚢胞腎を迅速に識別する早期診断マーカーにつながると考えられる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (23 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (3 results) Journal Article (9 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 9 results,  Open Access: 6 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] リール大学(フランス)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] リール大学(フランス)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] マッコリー大学(オーストラリア)

    • Related Report
      2022 Research-status Report
  • [Journal Article] Tolerable glycometabolic stress boosts cancer cell resilience through altered N-glycosylation and Notch signaling activation2024

    • Author(s)
      Iwamoto Shungo、Kobayashi Takashi、Hanamatsu Hisatoshi、Yokota Ikuko、Teranishi Yukiko、Iwamoto Akiho、Kitagawa Miyu、Ashida Sawako、Sakurai Ayane、Matsuo Suguru、Myokan Yuma、Sugimoto Aiyu、Ushioda Ryo、Nagata Kazuhiro、Gotoh Noriko、Nakajima Kazuki、Nishikaze Takashi、Furukawa Jun-ichi、Itano Naoki
    • Journal Title

      Cell Death & Disease

      Volume: 15 Issue: 1 Pages: 1-15

    • DOI

      10.1038/s41419-024-06432-z

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Splicing regulation of GFPT1 muscle-specific isoform and its roles in glucose metabolisms and neuromuscular junction2023

    • Author(s)
      Farshadyeganeh Paniz、Nazim Mohammad、Zhang Ruchen、Ohkawara Bisei、Nakajima Kazuki、Rahman Mohammad Alinoor、Nasrin Farhana、Ito Mikako、Takeda Jun-ichi、Ohe Kenji、Miyasaka Yuki、Ohno Tamio、Masuda Akio、Ohno Kinji
    • Journal Title

      iScience

      Volume: 26 Issue: 10 Pages: 107746-107746

    • DOI

      10.1016/j.isci.2023.107746

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cancer Malignancy Is Correlated with Upregulation of PCYT2-Mediated Glycerol Phosphate Modification of α-Dystroglycan2022

    • Author(s)
      Umezawa F, Natsume M, Fukusada S, Nakajima K, Yamasaki F, Kawashima H, Kuo CW, Khoo KH, Shimura T, Yagi H, Kato K.
    • Journal Title

      Int J Mol Sci.

      Volume: 23 Issue: 12 Pages: 6662-6662

    • DOI

      10.3390/ijms23126662

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Racial heterogeneity of IgA1 hinge-region O-glycoforms in patients with IgA nephropathy2022

    • Author(s)
      Ohyama Y, Yamaguchi H, Ogata S, Chiurlia S, Cox SN, Kouri NM, Stangou MJ, Nakajima K, Hayashi H, Inaguma D, Hasegawa M, Yuzawa Y, Tsuboi N, Renfrow MB, Novak J, Papagianni AA, Schena FP, Takahashi K.
    • Journal Title

      iScience

      Volume: 25 Issue: 11 Pages: 105223-105223

    • DOI

      10.1016/j.isci.2022.105223

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Treatment of tubular damage in high-fat-diet-fed obese mice using sodium-glucose co-transporter inhibitors2022

    • Author(s)
      Saitoh S, Takaki T, Nakajima K, Wo B, Terashima H, Shimo S, Nguyen HB, Thai TQ, Kumamoto K, Kunisawa K, Nagao S, Tojo A, Ohno N, Takahashi K.
    • Journal Title

      Plos One

      Volume: 18 Issue: 2 Pages: e0281770-e0281770

    • DOI

      10.1371/journal.pone.0281770

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hepatocellular carcinoma induces body mass loss in parallel with osmolyte and water retention in rats2022

    • Author(s)
      Kidoguchi Satoshi、Kitada Kento、Nakajima Kazuki、Nakano Daisuke、Ohsaki Hiroyuki、Kittikulsuth Wararat、Kobara Hideki、Masaki Tsutomu、Yokoo Takashi、Takahashi Kazuo、Titze Jens、Nishiyama Akira
    • Journal Title

      Life Sciences

      Volume: 289 Pages: 120192-120192

    • DOI

      10.1016/j.lfs.2021.120192

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Baseline uric acid levels and steady-state favipiravir concentrations are associated with occurrence of hyperuricemia among COVID-19 patients2022

    • Author(s)
      Koseki T, Nakajima K, Iwasaki H, Yamada S, Takahashi K, Doi Y, Mizuno T
    • Journal Title

      Int J Infect Dis

      Volume: 115 Pages: 218-223

    • DOI

      10.1016/j.ijid.2021.12.324

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] High-throughput N-glycan screening method for therapeutic antibodies using a microchip-based DNA analyzer: a promising methodology for monitoring monoclonal antibody N-glycosylation2021

    • Author(s)
      Kinoshita Mitsuhiro、Nakajima Kazuki、Yamamoto Sachio、Suzuki Shigeo
    • Journal Title

      Analytical and Bioanalytical Chemistry

      Volume: 413 Issue: 19 Pages: 4727-4738

    • DOI

      10.1007/s00216-021-03434-0

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Basigin deficiency prevents anaplerosis and ameliorates insulin resistance and hepatosteatosis.2021

    • Author(s)
      Ryuge A, Kosugi T, Maeda K, Banno R, Gou Y, Zaitsu K,Ito T, Sato Y, Hirayama A, Tsubota S, Honda T, Nakajima K, Ozaki T, Kondoh K, Takahashi K, Kato N, Ishimoto T, Soga T, Nakagawa T, Koike T, Arima H, Yuzawa Y, Minokoshi Y, Maruyama S, Kadomatsu K.
    • Journal Title

      JCI Insight.

      Volume: 6 Issue: 20

    • DOI

      10.1172/jci.insight.142464

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Platform for rapid plasma N-glycoproteomics using magnetic beads and application for biomarker discovery2023

    • Author(s)
      Kazuki Nakajima
    • Organizer
      Protein Metrics, Japanese User Group Meeting
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] ヒューマングライコームプロジェクト:ヒト疾患糖鎖関連カタログを作成する 迅速血漿グライコプロテオミクス基盤の検討2023

    • Author(s)
      半澤 健,村上 怜子,他那,早川 伸樹,鈴木 敦詞,門松 健治, 〇中嶋 和紀
    • Organizer
      第48回 日本医用マススペクトル学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Magnetic beads-based method of plasma N-glycoproteomics toward automated analysis2023

    • Author(s)
      〇Kazuki Nakajima, Ken Hanzawa, Reiko Murakami
    • Organizer
      2023 Society for Glycobiology Annual Meeting
    • Related Report
      2023 Annual Research Report
  • [Presentation] Screening and quantification of low abundance nucleotide sugars by HILIC-ESI-MS/MS to trace rare sugar-driven glycosylation2023

    • Author(s)
      Kazuki Nakajima
    • Organizer
      Glyco 26
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] HILI-ion mobility-ESI-MS/MSシステムにおける希少糖ヌクレオチドの探索2022

    • Author(s)
      中嶋和紀
    • Organizer
      第41回日本糖質学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] 糖異性体の分離技術を駆使した希少糖ヌクレオチドの探索2022

    • Author(s)
      中嶋和紀
    • Organizer
      第95回日本生化学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] High-throughput analytical system for tracing nucleotide sugar-driven glycosylation2022

    • Author(s)
      Kazuki Nakajiima
    • Organizer
      JSPS Core-to-Core Program, UGLIP Seminar
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] HILIC-ESI-MS/MSによる希少糖ヌクレオチドの探索2022

    • Author(s)
      中嶋和紀、木下充弘、星雅人、髙橋和男
    • Organizer
      第40回 日本糖質学会年会
    • Related Report
      2021 Research-status Report
  • [Remarks]

    • URL

      https://medical.jiji.com/topics/2621

    • Related Report
      2022 Research-status Report
  • [Remarks]

    • URL

      https://www.fujita-hu.ac.jp/news/j93sdv000000gdz0.html

    • Related Report
      2022 Research-status Report
  • [Patent(Industrial Property Rights)] 糖ペプチド試料の製造方法2024

    • Inventor(s)
      中嶋和紀、半澤健
    • Industrial Property Rights Holder
      中嶋和紀、半澤健
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2024-002980
    • Filing Date
      2024
    • Related Report
      2023 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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