Division of Nephrology and Laboratory on Pathophysiology of Uremia, G. Gaslini Children Hospital, Genoa, Italy.
Proteomics Clin Appl. 2008 Jul;2(7-8):956-63. doi: 10.1002/prca.200780157. Epub 2008 Jun 18.
Proteinuria is the hallmark of renal diseases and the characterization of the urinary protein composition may become an important source of information for diagnosis and research. So far, protein analysis in urine has been utilized for a generic individuation of site-specific defects (glomerular vs. tubular) but there is a need for an extension of proteomics to specific urinary biomarkers in selected clinical conditions. The identification of fragments of proteins in plasma and urine may increase the spectrum of urinary biomarkers. The unique speculative application so far proposed for protein fragments is nephrotic syndrome, and specifically focal segmental glomerulosclerosis, in which case they reflect intrinsic proteolysis occurring in plasma and represent surrogate biomarkers of the disease activity. Albumin is probably the most studied protein. Several of the albumin fragments present a peculiar distribution of the fingerprint peptide pattern containing both the N-terminal region and the C-terminal domain with a complete lack of any MS signals for the internal sequence region. Their characterization utilizing new strategies based on 2-D nondenaturing electrophoresis is now in progress. Studies on a direct characterization of proteases in plasma and urine will also define the participation of proteases to the genesis of renal diseases.
蛋白尿是肾脏疾病的标志，尿液中蛋白质成分的特征可能成为诊断和研究的重要信息来源。到目前为止，尿液中的蛋白质分析已经被用于特定部位缺陷（肾小球与肾小管）的一般鉴别，但需要将蛋白质组学扩展到特定的临床条件下的特定尿液生物标志物。在血浆和尿液中鉴定蛋白质片段可以增加尿液生物标志物的范围。迄今为止，唯一提出的用于蛋白质片段的推测性应用是肾病综合征，特别是局灶节段性肾小球硬化症，在这种情况下，它们反映了血浆中发生的内在蛋白水解，并代表疾病活动的替代生物标志物。白蛋白可能是研究最多的蛋白质。存在一些具有特征性分布的白蛋白片段，这些片段的指纹肽模式既包含 N 端区域又包含 C 端结构域，完全没有任何内部序列区域的 MS 信号。现在正在利用基于二维非变性电泳的新策略对其进行特征描述。对血浆和尿液中蛋白酶的直接特征描述的研究也将确定蛋白酶参与肾脏疾病的发生。
