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从大鼠和小鼠尿液样本中纯化的外泌体样小泡中的候选生物标志物。

Candidate biomarkers in exosome-like vesicles purified from rat and mouse urine samples.

机构信息

Metabolomics Unit, CICbioGUNE, CIBERehd, Bizkaia Technology Park, Derio, Bizkaia, Spain.

出版信息

Proteomics Clin Appl. 2010 Apr;4(4):416-25. doi: 10.1002/prca.200900103.

Abstract

PURPOSE

There is a compelling clinical imperative to identify discerning molecular biomarkers of hepatic disease in order to inform the diagnosis, prognosis and treatment.

EXPERIMENTAL DESIGN

We have investigated the proteome of urinary vesicles present in urine samples obtained from experimental models for the study of liver injury, as an approach for identifying potential biomarkers for hepatic disease.

RESULTS

The biochemical and proteomic characterization of highly purified exosome-like urinary vesicles has identified 28 proteins previously unreported in these vesicles, and many that have been previously associated with diseases, such as the prion-related protein. Furthermore, in urine samples from D-galactosamine-treated rats, a well-characterized experimental model for acute liver injury, we have detected a severe reduction in some proteins that normally are clearly detected in urinary vesicles. Finally, differential protein content on urinary vesicles from a mouse model for chronic liver injury has been also identified.

CONCLUSIONS AND CLINICAL RELEVANCE

Our results argue positively that urinary vesicles could be a source for identifying non-invasive biomarkers of liver injury. We proposed some proteins such as Cd26, Cd81, Slc3A1 and Cd10 that have been found to be differentially expressed in urinary vesicles from some of the analyzed models as potential biomarkers for liver injury.

摘要

目的

为了在诊断、预后和治疗中提供信息,迫切需要识别出有区别的肝脏疾病的分子生物标志物。

实验设计

我们研究了尿液样本中存在的尿囊素的蛋白质组,这些样本来自肝脏损伤研究的实验模型,作为鉴定潜在肝脏疾病生物标志物的一种方法。

结果

对高度纯化的类外泌体尿囊素进行生化和蛋白质组学分析,鉴定出了 28 种以前在这些囊泡中未报道过的蛋白质,其中许多与疾病有关,如朊病毒相关蛋白。此外,在半乳糖胺处理的大鼠尿液样本中,一种急性肝损伤的典型实验模型,我们检测到一些通常在尿囊素中明显检测到的蛋白质严重减少。最后,还鉴定出了慢性肝损伤小鼠模型中尿囊素的差异蛋白含量。

结论和临床相关性

我们的结果有力地证明,尿囊素可能是鉴定肝损伤非侵入性生物标志物的来源。我们提出了一些蛋白质,如 Cd26、Cd81、Slc3A1 和 Cd10,它们在一些分析模型的尿囊素中被发现差异表达,可作为肝损伤的潜在生物标志物。

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