Urine proteome of autosomal dominant polycystic kidney disease patients.
Urine proteome of autosomal dominant polycystic kidney disease patients.
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DOI：
10.1186/1559-0275-9-13
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发表时间：
2012-12-11
影响因子：
3.8
通讯作者：
Dadlez M
中科院分区：
文献类型：
--
作者：
Bakun M;Niemczyk M;Domanski D;Jazwiec R;Perzanowska A;Niemczyk S;Kistowski M;Fabijanska A;Borowiec A;Paczek L;Dadlez M
常染色体显性遗传性多囊肾病(ADPKD)占终末期肾病的10%。早期诊断，尤其是对潜在的快速进展者的早期诊断将有助于有效的治疗计划。尿排泄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很有前途的领域。然而，到目前为止，对ADPKD蛋白质组指纹图谱的研究仅限于低相对分子质量组分。本研究的目的是为了在建立临床有用的疾病标志物小组之前，对ADPKD人群尿蛋白质组的高分子量部分与健康对照组进行比较，以期在建立临床有用的疾病标志物小组之前，对健康和疾病中的人尿蛋白质组进行详尽的描述。我们用无胶相对定量的方法分析了30例ADPKD患者和一名健康对照组的尿Retentate(>；10 kDa截止值)的蛋白质组成。我们已经确定了一个ADPKD特有的足迹，它由155个蛋白组成，在ADPKD患者的尿液中显著上调或下调。我们发现，除了已知的胶原蛋白和细胞外基质成分外，补体系统的蛋白质、载脂蛋白、蛇毒蛋白、几种生长因子也发生了变化。对于这些蛋白质的一个子集，我们已经使用另一种分析技术确认了结果。研究结果为进一步研究这些差异的发病机制和建立蛋白质组预后标记物小组提供了依据。
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.