An Attempt to Understand Kidney's Protein Handling Function by Comparing Plasma and Urine Proteomes

BackgroundWith the help of proteomics technology, the human plasma and urine proteomes, which closely represent the protein compositions of the input and output of the kidney, respectively, have been profiled in much greater detail by different research teams. Many datasets have been accumulated to form “reference profiles” of the plasma and urine proteomes. Comparing these two proteomes may help us understand the protein handling aspect of kidney function in a way, however, which has been unavailable until the recent advances in proteomics technology.
Methodology/Principal FindingsAfter removing secreted proteins downstream of the kidney, 2611 proteins in plasma and 1522 in urine were identified with high confidence and compared based on available proteomic data to generate three subproteomes, the plasma-only subproteome, the plasma-and-urine subproteome, and the urine-only subproteome, and they correspond to three groups of proteins that are handled in three different ways by the kidney. The available experimental molecular weights of the proteins in the three subproteomes were collected and analyzed. Since the functions of the overrepresented proteins in the plasma-and-urine subproteome are probably the major functions that can be routinely regulated by excretion from the kidney in physiological conditions, Gene Ontology term enrichment in the plasma-and-urine subproteome versus the whole plasma proteome was analyzed. Protease activity, calcium and growth factor binding proteins, and coagulation and immune response-related proteins were found to be enriched.
Conclusion/SignificanceThe comparison method described in this paper provides an illustration of a new approach for studying organ functions with a proteomics methodology. Because of its distinctive input (plasma) and output (urine), it is reasonable to predict that the kidney will be the first organ whose functions are further elucidated by proteomic methods in the near future. It can also be anticipated that there will be more applications for proteomics in organ function research.

【研究背景】借助蛋白质组学（proteomics）技术，不同研究团队已对人类血浆蛋白质组与尿液蛋白质组进行了更为精细的图谱绘制——二者分别对应肾脏的输入与输出的蛋白质组成。目前已有大量数据集积累，形成了血浆与尿液蛋白质组的“参考图谱”。长期以来，通过对比这两种蛋白质组以解析肾脏蛋白质处理功能的思路受限于技术水平，而近年来蛋白质组学技术的突破为该方向提供了可行路径。
【方法/主要结果】本研究去除肾脏下游分泌蛋白后，通过高可信度鉴定得到血浆蛋白2611种、尿液蛋白1522种，并基于现有蛋白质组学数据开展对比分析，最终得到三类亚蛋白质组（subproteomes）：仅血浆亚蛋白质组、血浆-尿液共有亚蛋白质组、仅尿液亚蛋白质组，三者分别对应肾脏以三种不同方式处理的蛋白质群。研究人员收集并分析了三类亚蛋白质组中蛋白质的实验分子量数据。鉴于生理状态下，血浆-尿液共有亚蛋白质组中富集的蛋白质功能，大概率是肾脏通过排泄作用常规调控的核心功能，因此本研究针对该亚蛋白质组相较于全血浆蛋白质组的基因本体（Gene Ontology）术语富集情况开展了分析。结果显示，蛋白酶活性相关蛋白、钙结合与生长因子结合蛋白，以及凝血与免疫应答相关蛋白均呈现富集状态。
【结论/意义】本研究提出的对比方法，为利用蛋白质组学技术研究器官功能提供了一种全新的示范范式。由于肾脏具有独特的“输入（血浆）-输出（尿液）”生理特征，可合理预测：在不久的将来，肾脏将成为首个通过蛋白质组学方法进一步阐明功能的器官。同时可以预见，蛋白质组学技术在器官功能研究领域将拥有更为广阔的应用前景。