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Urolithiasis diagnosis and recurrence prediction method by urinary aberrant glycosylation of osteopontin and related glycosyltransferases

Research Project

Project/Area Number 19K18570
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56030:Urology-related
Research InstitutionTohoku Medical and Pharmaceutical University

Principal Investigator

Anan Go  東北医科薬科大学, 医学部, 助教 (70816222)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords尿路結石 / オステオポンチン / 糖鎖生物学 / 糖鎖 / 糖転移酵素
Outline of Research at the Start

尿路結石症は生活習慣病の一疾患であり、罹患数が大変多く再発率の高い疾患であるが、尿路結石症の成因の究明と再発予防法の確立はされていない。今回、尿路結石の形成過程に必要なオステオポンチンという糖蛋白質に着目し、オステオポンチンの糖鎖の機能と尿路結石形成との関連を調査する。オステオポンチン糖鎖変異が尿路結石形成過程にどのように関連しているのかを調べ、尿路結石診断、再発予測法の確立を目標としている。

Outline of Final Research Achievements

Osteopontin (OPN) is a matrix glycoprotein of urinary calculi. This study aims to identify the role of aberrant glycosylation of OPN in urolithiasis. We retrospectively measured urinary glycosylated OPN normalized by urinary full-length-OPN (uFL-OPN) levels in 110 urolithiasis patients and 157 healthy volunteers (HVs). The uFL-OPN levels were measured using enzyme-linked immunosorbent assay and glycosylated OPN was measured using a lectin array and lectin blotting.
In the study, we found that the uFL-OPN adjusted urine total protein was significantly lower in stone forming patients than in HVs (p < 0.001) and that urinary Gal3C-S-OPN/uFL-OPN level was significantly higher in stone forming patients than in HVs (p < 0.001). Immunoblotting and lectin blotting analysis showed that the band intensity of uFL-OPN in the HVs was higher than that of the uFL-OPN in the stone forming patients, whereas the band intensity of LEL reactive OPN clearly increased in stone forming urolithiasis patients.

Academic Significance and Societal Importance of the Research Achievements

尿路結石形成に必須とされている1つがオステオポンチン(OPN)である。OPNは糖タンパク質である。これまで、尿路結石の研究分野においてOPNの糖鎖構造の変化と結石形成との関連についての研究はない。
今回、私たちはOPNの糖鎖に着目した。尿路結石患者では健常者と比較して尿中OPN濃度は低下するにもかかわらず、糖鎖変異OPN(Gal3C-S-OPN)とポリラクトサミンOPNが有意に増加した。以上より、尿路結石患者の尿中OPNの糖鎖構造変化が明らかとなった。この糖鎖変異OPNが結石形成にどのように関わっているのか、糖鎖変異OPNの機能解析を含めて今後検討が必要である。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (9 results)

All 2021 2020 2019

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

  • [Journal Article] 尿路結石形成に関与する糖鎖変異オステオポンチンの検索2021

    • Author(s)
      阿南 剛、米山 徹、野呂大輔、飛澤悠葵、畠山真吾、米山美穂子、山本勇人、今井 篤、米山高弘、橋本安弘、佐藤 信、大山 力
    • Journal Title

      日本内分泌学会雑誌

      Volume: 97 Pages: 47-49

    • NAID

      130008069561

    • Related Report
      2021 Annual Research Report
  • [Journal Article] The Impact of Glycosylation of Osteopontin on Urinary Stone Formation2019

    • Author(s)
      Anan Go、Yoneyama Tohru、Noro Daisuke、Tobisawa Yuki、Hatakeyama Shingo、Sutoh Yoneyama Mihoko、Yamamoto Hayato、Imai Atsushi、Iwamura Hiromichi、Kohada Yuki、Mikami Jotaro、Ito Jun、Kaiho Yasuhiro、Yoneyama Takahiro、Hashimoto Yasuhiro、Sato Makoto、Ohyama Chikara
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 1 Pages: 93-93

    • DOI

      10.3390/ijms21010093

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 腎臓結石形成に関与する糖鎖変異オステオポンチンの同定2021

    • Author(s)
      阿南 剛
    • Organizer
      第64回日本腎臓学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Identification of aberrant glycosylation of osteopontin on urinary stone formation2021

    • Author(s)
      Go Anan
    • Organizer
      European Association of Urology (EAU2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification of aberrant glycosylation of osteopontin on urinary stone formation2021

    • Author(s)
      Go Anan
    • Organizer
      American Urological Associaction(AUA2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 尿路結石と糖鎖(オステオポンチン糖鎖変異の検索)2020

    • Author(s)
      阿南 剛
    • Organizer
      第108回日本泌尿器学会総会(シンポジウム)
    • Related Report
      2020 Research-status Report
  • [Presentation] Identification of aberrant glycosylation of osteopontin in urinary stone former patients as a urolithiasis biomarker2019

    • Author(s)
      Go Anan
    • Organizer
      American Urological Associaction 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 尿路結石形成に関与する尿中糖鎖変異オステオポンチン(PolyLac-OPN)の同定2019

    • Author(s)
      阿南 剛
    • Organizer
      107回日本泌尿器科学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] オステオポンチン糖鎖変異-PolyLacNAcオステオポンチンの結石バイオマーカーの可能性-2019

    • Author(s)
      阿南 剛
    • Organizer
      29回日本尿路結石症学会学術集会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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