Department II of Internal Medicine University of Cologne Faculty of Medicine and University Hospital Cologne Cologne Germany.
III. Department of Medicine University Medical Center Hamburg-Eppendorf Hamburg Germany.
J Extracell Vesicles. 2020 Oct;10(1):e12026. doi: 10.1002/jev2.12026. Epub 2020 Nov 19.
Kidney transplantation is the preferred renal replacement therapy available. Yet, long-term transplant survival is unsatisfactory, partially due to insufficient possibilities of longitudinal monitoring and understanding of the biological processes after transplantation. Small urinary extracellular vesicles (suEVs) - as a non-invasive source of information - were collected from 22 living donors and recipients. Unbiased proteomic analysis revealed temporal patterns of suEV protein signature and cellular processes involved in both early response and longer-term graft adaptation. Complement activation was among the most dynamically regulated components. This unique atlas of the suEV proteome is provided through an online repository allowing dynamic interrogation by the user. Additionally, a correlative analysis identified putative prognostic markers of future allograft function. One of these markers - phosphoenol pyruvate carboxykinase (PCK2) - could be confirmed using targeted MS in an independent validation cohort of 22 additional patients. This study sheds light on the impact of kidney transplantation on urinary extracellular vesicle content and allows the first deduction of early molecular processes in transplant biology. Beyond that our data highlight the potential of suEVs as a source of biomarkers in this setting.
肾移植是首选的肾脏替代治疗方法。然而，长期的移植存活率并不理想，部分原因是缺乏对移植后生物过程进行纵向监测和了解的可能性。从小尿细胞外囊泡（suEVs）中采集了 22 个活体供体和受者的非侵入性信息源。无偏蛋白组分析揭示了 suEV 蛋白特征的时间模式以及早期反应和长期移植物适应所涉及的细胞过程。补体激活是最具动态调节的成分之一。通过在线存储库提供了这个独特的 suEV 蛋白质组图谱，允许用户进行动态查询。此外，相关性分析确定了未来同种异体移植物功能的潜在预后标志物。其中一个标志物——磷酸烯醇丙酮酸羧激酶（PCK2）——可以在 22 名额外患者的独立验证队列中使用靶向 MS 进行确认。这项研究揭示了肾移植对尿细胞外囊泡含量的影响，并允许首次推断移植生物学中的早期分子过程。除此之外，我们的数据还强调了 suEVs 在这种情况下作为生物标志物来源的潜力。
