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

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18570
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Tohoku 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
• Keywords: 尿路結石 / オステオポンチン / 糖鎖生物学

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.

Free Research Field

尿路結石

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。