Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
Proteomics Clin Appl. 2015 Dec;9(11-12):1053-68. doi: 10.1002/prca.201400201. Epub 2015 Aug 11.
Diseases of the glomerular filter of the kidney are a leading cause of end-stage renal failure. The kidney filter is localized within the renal glomeruli, small microvascular units that are responsible for ultrafiltration of about 180 liters of primary urine every day. The renal filter consists of three layers, fenestrated endothelial cells, glomerular basement membrane, and the podocytes, terminally differentiated, arborized epithelial cells. This review demonstrates the use of proteomics to generate insights into the regulation of the renal filtration barrier at a molecular level. The advantages and disadvantages of different glomerular purification methods are examined, and the technical limitations that have been significantly improved by in silico or biochemical approaches are presented. We also comment on phosphoproteomic studies that have generated considerable molecular-level understanding of the physiological regulation of the kidney filter. Lastly, we conclude with an analysis of urinary exosomes as a potential filter-derived resource for the noninvasive discovery of glomerular disease mechanisms.
肾脏肾小球滤器疾病是终末期肾衰竭的主要原因。肾脏滤器位于肾脏肾小球内，肾小球是负责每天超滤液约 180 升原尿的微小微血管单位。肾脏滤器由三层组成，有孔的内皮细胞、肾小球基底膜和足细胞，足细胞是终末分化的树枝状上皮细胞。这篇综述展示了蛋白质组学在分子水平上生成对肾脏滤过屏障调节的认识的应用。检查了不同肾小球净化方法的优缺点，并介绍了通过计算机模拟或生化方法显著改进的技术局限性。我们还评论了磷酸化蛋白质组学研究，这些研究对肾脏滤器的生理调节有了相当大的分子水平的理解。最后，我们分析了尿外泌体作为一种潜在的滤器衍生资源，用于非侵入性发现肾小球疾病机制。
