Hoorn Ewout J, Pisitkun Trairak, Zietse Robert, Gross Peter, Frokiaer Joergen, Wang Nam Sun, Gonzales Patricia A, Star Robert A, Knepper Mark A
Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1603, USA.
Nephrology (Carlton). 2005 Jun;10(3):283-90. doi: 10.1111/j.1440-1797.2005.00387.x.
Recent progress in biotechnology offers the promise of better medical care at lower costs. Among the techniques that show the greatest promise is mass spectrometry of proteins, which can identify proteins present in body fluids and tissue specimens at a large scale. Because urine can be collected in large amounts in a non-invasive fashion, the potential exists to use mass spectrometry to discover urinary biomarkers that are early predictors of renal disease, or useful in making therapeutic choices. Recently, the authors demonstrated that both membrane proteins and cytosolic proteins from renal epithelia are highly enriched in low-density urinary structures identified as exosomes. Exosomes were found to contain many disease-associated proteins including aquaporin-2, polycystin-1, podocin, non-muscle myosin II, angiotensin-converting enzyme, Na+ K+ 2Cl- cotransporter (NKCC2), thiazide-sensitive Na-Cl cotransporter (NCC), and epithelial sodium channel (ENaC). Potentially, other disease biomarkers could be discovered by mass spectrometry-based proteomic studies in well-defined patient populations. Herein is described the advantages of using urinary exosomes as a starting material for biomarker discovery. In addition, the purpose of this review is to present an overall strategy for biomarker discovery in urine using exosomes and for developing cost-effective clinical assays for these biomarkers, which can potentially be used for early detection of disease, as a means of differential diagnosis, or as a means of guiding therapy. Finally, potential barriers that need to be overcome before urinary proteomics can be applied clinically, are emphasized.
生物技术的最新进展为以更低成本提供更好的医疗服务带来了希望。在最具潜力的技术中，蛋白质质谱分析脱颖而出，它能够大规模鉴定体液和组织样本中存在的蛋白质。由于尿液可以通过非侵入性方式大量收集，因此利用质谱分析来发现可作为肾脏疾病早期预测指标或有助于做出治疗选择的尿液生物标志物具有潜力。最近，作者证明肾上皮细胞的膜蛋白和胞质蛋白在被鉴定为外泌体的低密度尿液结构中高度富集。研究发现外泌体含有许多与疾病相关的蛋白质，包括水通道蛋白 -2、多囊蛋白 -1、足突蛋白、非肌肉肌球蛋白 II、血管紧张素转换酶、钠 - 钾 -2 氯共转运蛋白（NKCC2）、噻嗪类敏感钠氯共转运蛋白（NCC）和上皮钠通道（ENaC）。潜在地，通过基于质谱的蛋白质组学研究，在明确界定的患者群体中可能发现其他疾病生物标志物。本文描述了使用尿液外泌体作为生物标志物发现起始材料的优势。此外，本综述的目的是提出一种利用外泌体在尿液中发现生物标志物以及开发这些生物标志物经济高效临床检测方法的总体策略，这些方法可潜在地用于疾病的早期检测、作为鉴别诊断手段或作为指导治疗的手段。最后，强调了在尿液蛋白质组学能够临床应用之前需要克服的潜在障碍。
