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尿液糖蛋白谱揭示了慢性肾病的新标志物。

Urine glycoprotein profile reveals novel markers for chronic kidney disease.

作者信息

Vivekanandan-Giri Anuradha, Slocum Jessica L, Buller Carolyn L, Basrur Venkatesha, Ju Wenjun, Pop-Busui Rodica, Lubman David M, Kretzler Matthias, Pennathur Subramaniam

机构信息

Division of Nephrology, University of Michigan, Ann Arbor, MI 48105, USA.

出版信息

Int J Proteomics. 2011;2011:214715. doi: 10.1155/2011/214715. Epub 2011 Oct 10.

Abstract

Chronic kidney disease (CKD) is a significant public health problem, and progression to end-stage renal disease leads to dramatic increases in morbidity and mortality. The mechanisms underlying progression of disease are poorly defined, and current noninvasive markers incompletely correlate with disease progression. Therefore, there is a great need for discovering novel markers for CKD. We utilized a glycoproteomic profiling approach to test the hypothesis that the urinary glycoproteome profile from subjects with CKD would be distinct from healthy controls. N-linked glycoproteins were isolated and enriched from the urine of healthy controls and subjects with CKD. This strategy identified several differentially expressed proteins in CKD, including a diverse array of proteins with endopeptidase inhibitor activity, protein binding functions, and acute-phase/immune-stress response activity supporting the proposal that inflammation may play a central role in CKD. Additionally, several of these proteins have been previously linked to kidney disease implicating a mechanistic role in disease pathogenesis. Collectively, our observations suggest that the human urinary glycoproteome may serve as a discovery source for novel mechanism-based biomarkers of CKD.

摘要

慢性肾脏病(CKD)是一个重大的公共卫生问题,疾病进展至终末期肾病会导致发病率和死亡率急剧上升。疾病进展的潜在机制尚不明确,目前的非侵入性标志物与疾病进展的相关性并不完全。因此,迫切需要发现CKD的新型标志物。我们采用了一种糖蛋白质组分析方法来验证这一假设,即CKD患者的尿糖蛋白质组图谱与健康对照者不同。从健康对照者和CKD患者的尿液中分离并富集N-连接糖蛋白。该策略鉴定出了CKD中几种差异表达的蛋白质,包括一系列具有内肽酶抑制活性、蛋白质结合功能以及急性期/免疫应激反应活性的蛋白质,这支持了炎症可能在CKD中起核心作用的观点。此外,这些蛋白质中有几种先前已与肾脏疾病相关联,提示其在疾病发病机制中具有机制性作用。总体而言,我们的观察结果表明,人类尿糖蛋白质组可能作为基于机制的CKD新型生物标志物的发现来源。

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