The Impact of Glycosylation of Osteopontin on Urinary Stone Formation

The Impact of Glycosylation of Osteopontin on Urinary Stone Formation
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DOI:
10.3390/ijms21010093
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发表时间:
2020-01-01
影响因子:
5.6
通讯作者:
Ohyama, Chikara
Ohyama, Chikara
中科院分区:
生物学2区
文献类型:
--
作者:
Anan, Go;Yoneyama, Tohru;Ohyama, Chikara

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骨桥蛋白(OPN)是尿路结石的基质糖蛋白。本研究旨在确定OPN异常糖基化在尿石症中的作用。我们回顾性地测量了110例尿石症患者和157名健康志愿者的尿糖基化OPN,并对21名患者进行了前瞻性随访。采用酶联免疫吸附法测定尿全长OPN水平,采用凝集素阵列和凝集素印迹法测定糖基化OPN水平。使用受试者操作特征曲线下的面积对检测结果进行评估,以区分结石形成性尿石症患者。在回顾性队列中,尿中Gal3C-S凝集素反应- (Gal3C-S-) OPN/全长OPN在成石性尿石症患者中显著高于健康志愿者(p < 0.0001),具有良好的鉴别性(AUC, 0.953), 90%的敏感性和92%的特异性。番茄凝集素对尿全长opn的分析表明,结石形成性尿石症患者的尿全长opn具有多lacnac结构,这在健康志愿者中没有观察到。在前瞻性纵向随访研究中,92.8%的无结石尿石组在输尿管镜碎石(URS)后gal3g -s - opn /全长opn水平低于截断值,而71.4%的残余结石尿石组在URS后未出现下降。因此,Gal3C-S-OPN/全长opn水平可作为尿石症的生物标志物。
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 110 urolithiasis patients and 157 healthy volunteers and 21 patients were prospectively longitudinal follow-up during stone treatment. The urinary full-length-OPN levels were measured using enzyme-linked immunosorbent assay and glycosylated OPN was measured using a lectin array and lectin blotting. The assays were evaluated using the area under the receiver operating characteristics curve to discriminate stone forming urolithiasis patients. In the retrospective cohort, urinary Gal3C-S lectin reactive- (Gal3C-S-) OPN/full-length-OPN, was significantly higher in the stone forming urolithiasis patients than in the healthy volunteers (p < 0.0001), with good discrimination (AUC, 0.953), 90% sensitivity, and 92% specificity. The Lycopersicon esculentum lectin analysis of urinary full-length-OPN showed that urinary full-length-OPN in stone forming urolithiasis patients had a polyLacNAc structure that was not observed in healthy volunteers. In the prospective longitudinal follow-up study, 92.8% of the stone-free urolithiasis group had Gal3C-S-OPN/full-length-OPN levels below the cutoff value after ureteroscopic lithotripsy (URS), whereas 71.4% of the residual-stone urolithiasis group did not show decreased levels after URS. Therefore, Gal3C-S-OPN/full-length-OPN levels could be used as a urolithiasis biomarker.