Study on forcusing glycosylation of osteopontin for urinary stone diagnosis and development of preventive medicine.

• Project/Area Number: 18K16718
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Hirosaki University
• Principal Investigator: Noro Daisuke 弘前大学, 医学研究科, 客員研究員 (60793635)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: オステオポンチン / 糖鎖 / レクチン / 尿路結石

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 levels in 157 urolithiasis patients and 110 healthy volunteers and 21 patients were prospectively longitudinal follow-up during stone treatment. This study showed that OPN concentration in urine was significantly lower in stone forming patients than in HVs. However, Gal3C-S-OPN was significantly increased in stone forming patients, which suggested its potential as a biomarker of urolithiasis formation. Therefore, Gal3C-S-OPN/uFL-OPN levels might be a biomarker of stone formation. Urolithiasis is a disease with a high rate of recurrence. Gal3C-S-OPN might be useful as a predictor of recurrence, and elucidation of the mechanism of urinary stone recurrence may lead to prevention.

Academic Significance and Societal Importance of the Research Achievements

我が国では100人中6人、欧米では20人にも達する国もみられ、生産年齢の男性に多く、その成因の究明と再発予防法の確立は急務である。本研究で得られた成果として、尿路結石患者では健常者と比較して、尿中OPN濃度は有意に減少したにも関わらず糖鎖変異OPN(Gal3C-S-OPN)が有意に増加していた。尿路結石の有無とGal3C-S-OPN量が関連していることから、OPN糖鎖変異が尿路結石診断、再発予測に関する糖鎖性バイオマーカーに成り得る可能性が示唆された。尿路結石は、再発が多く結石形成の再発予測ができれば、患者のQOLを改善するバイオマーカーとなり、社会的意義は、非常に大きい。

Research Products

• [Journal Article] The Impact of Glycosylation of Osteopontin on Urinary Stone Formation (2019)
  • 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 Pages: 93-93
  • DOI: 10.3390/ijms21010093
  • Peer Reviewed / Open Access