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The Novel Diagnostic Biomarkers for Focal Segmental Glomerulosclerosis

机译：局灶性节段性肾小球硬化症的新型诊断生物标志物

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Background. Focal segmental glomerulosclerosis (FSGS) is a glomerular injury with various pathogenic mechanisms. Urine proteome panel might help in noninvasive diagnosis and better understanding of pathogenesis of FSGS.Method. We have analyzed the urine sample of 11 biopsy-proven FSGS subjects, 8 healthy controls, and 6 patients with biopsy-proven IgA nephropathy (disease controls) by means of liquid chromatography tandem mass spectrometry (nLC-MS/MS). Multivariate analysis of quantified proteins was performed by principal component analysis (PCA) and partial least squares (PLS).Results. Of the total number of 389 proteins, after multivariate analysis and additional filter criterion and comparing FSGS versus IgA nephropathy and healthy subjects, 77 proteins were considered as putative biomarkers of FSGS. CD59, CD44, IBP7, Robo4, and DPEP1 were the most significant differentially expressed proteins. These proteins are involved in pathogenic pathways: complement pathway, sclerosis, cell proliferation, actin cytoskeleton remodeling, and activity of TRPC6.There was complete absence of DPEP1 in urine proteome of FSGS subjects compared with healthy and disease controls. DPEP1 acts via leukotrienes on TRPC6 and results in increased podocyte motility and proteinuria.Conclusion. The results suggest a panel of candidate biomarkers for noninvasive diagnosis of FSGS, while complete absence of DPEP1 might represent a novel marker of FSGS.
机译：背景。局灶性节段性肾小球硬化症（FSGS）是一种具有多种致病机制的肾小球损伤。尿蛋白组可能有助于无创诊断和更好地了解FSGS的发病机理。我们已经通过液相色谱串联质谱法（nLC-MS / MS）分析了11名经活检证实的FSGS受试者，8名健康对照和6名经活检证实的IgA肾病（疾病对照）的尿液样本。通过主成分分析（PCA）和偏最小二乘（PLS）对定量蛋白质进行多变量分析。在389种蛋白质的总数中，经过多变量分析和其他过滤标准并比较FSGS与IgA肾病和健康受试者后，有77种蛋白质被认为是FSGS的假定生物标记。 CD59，CD44，IBP7，Robo4和DPEP1是最重要的差异表达蛋白。这些蛋白质与致病途径有关：补体途径，硬化，细胞增殖，肌动蛋白细胞骨架重塑和TRPC6活性。与健康和疾病对照相比，FSGS受试者的尿蛋白质组中完全没有DPEP1。 DPEP1通过白三烯作用于TRPC6并导致足细胞运动性和蛋白尿增加。结果表明一组候选生物标志物可用于FSGS的非侵入性诊断，而完全不存在DPEP1可能代表FSGS的新标志物。

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