Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5A, 02-106, Warsaw, Poland.
Clin Proteomics. 2012 Dec 11;9(1):13. doi: 10.1186/1559-0275-9-13.
Autosomal dominant polycystic kidney disease (ADPKD) is responsible for 10% of cases of the end stage renal disease. Early diagnosis, especially of potential fast progressors would be of benefit for efficient planning of therapy. Urine excreted proteome has become a promising field of the search for marker patterns of renal diseases including ADPKD. Up to now however, only the low molecular weight fraction of ADPKD proteomic fingerprint was studied. The aim of our study was to characterize the higher molecular weight fraction of urinary proteome of ADPKD population in comparison to healthy controls as a part of a general effort aiming at exhaustive characterization of human urine proteome in health and disease, preceding establishment of clinically useful disease marker panel.
We have analyzed the protein composition of urine retentate (>10 kDa cutoff) from 30 ADPKD patients and an appropriate healthy control group by means of a gel-free relative quantitation of a set of more than 1400 proteins. We have identified an ADPKD-characteristic footprint of 155 proteins significantly up- or downrepresented in the urine of ADPKD patients. We have found changes in proteins of complement system, apolipoproteins, serpins, several growth factors in addition to known collagens and extracellular matrix components. For a subset of these proteins we have confirmed the results using an alternative analytical technique.
Obtained results provide basis for further characterization of pathomechanism underlying the observed differences and establishing the proteomic prognostic marker panel.
常染色体显性多囊肾病(ADPKD)占终末期肾病的 10%。早期诊断,特别是对潜在快速进展者的诊断,将有利于有效规划治疗。尿液外泌体蛋白质组已成为寻找包括 ADPKD 在内的肾脏疾病标志物模式的一个有前途的领域。然而,迄今为止,仅研究了 ADPKD 蛋白质组指纹图谱的低分子量部分。我们研究的目的是描述 ADPKD 人群尿液蛋白质组的高分子量部分与健康对照组的特征,这是全面描述健康和疾病人群尿液蛋白质组的一部分,旨在建立临床有用的疾病标志物面板之前。
我们通过对超过 1400 种蛋白质进行无胶相对定量分析,分析了 30 名 ADPKD 患者和适当的健康对照组尿液截留物(>10 kDa 截止值)的蛋白质组成。我们鉴定出 ADPKD 患者尿液中 155 种蛋白质明显上调或下调的 ADPKD 特征性特征。我们发现补体系统、载脂蛋白、丝氨酸蛋白酶抑制剂、几种生长因子以及已知的胶原蛋白和细胞外基质成分的变化。对于其中一些蛋白质,我们使用另一种分析技术证实了结果。
获得的结果为进一步阐明观察到的差异的发病机制以及建立蛋白质组预后标志物面板提供了基础。