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Changes of protein levels in human urine reflect the dysregulation of signaling pathways of chronic kidney disease and its complications
Scientific Reports ( IF 3.8 ) Pub Date : 2020-11-27 , DOI: 10.1038/s41598-020-77916-z
Yiming Hao 1 , Luis Tanon Reyes 2 , Robert Morris 2 , Yifeng Xu 1 , Yiqin Wang 1 , Feng Cheng 2
Affiliation  

The increasing prevalence of chronic kidney disease (CKD) seriously is threatening human health and overall quality of life. The discovery of biomarkers of pathogenesis of CKD and the associated complications are very important for CDK diagnosis and treatment. In this paper, urine protein biomarkers were investigated because urine sample collection is convenient and non-invasive. We analyzed the protein concentrations in the urine of CKD patients and extracted abnormal protein signals comparing with the healthy control groups. The enriched signaling pathways that may characterize CKD pathology were identified from these proteins. We applied surface-enhanced laser desorption and ionization time of flight mass spectrometry technology to detect different protein peaks in urine samples from patients with CKD and healthy controls. We searched the proteins corresponding to protein peaks through the UniProt database and identified the signaling pathways of CKD and its complications by using the NIH DAVID database. 42 low abundance proteins and 46 high abundance proteins in the urine samples from CKD patients were found by comparing with healthy controls. Seven KEGG pathways related to CKD and its complications were identified from the regulated proteins. These pathways included chemokine signaling pathway, cytokine–cytokine receptor interaction, oxidative phosphorylation, cardiac muscle contraction, Alzheimer’s disease, Parkinson's disease, and salivary secretion. In CKD stages 2, 3, 4, and 5, five proteins showed significantly differential abundances. The differential protein signals and regulated signaling pathways will provide new insight for the pathogenesis of CKD and its complications. These altered proteins may also be used as novel biomarkers for the noninvasive and convenient diagnosis methods of CKD and its complications through urine testing in the future.



中文翻译:

人体尿液中蛋白质水平的变化反映了慢性肾脏病及其并发症的信号通路失调

慢性肾脏病(CKD)患病率不断上升,严重威胁着人类健康和整体生活质量。CKD发病机制及相关并发症的生物标志物的发现对于CDK的诊断和治疗非常重要。在本文中,由于尿液样本采集方便且无创,因此对尿蛋白生物标志物进行了研究。我们分析了 CKD 患者尿液中的蛋白质浓度,并提取与健康对照组相比的异常蛋白质信号。从这些蛋白质中鉴定出可能表征 CKD 病理学特征的丰富信号通路。我们应用表面增强激光解吸和电离飞行时间质谱技术来检测 CKD 患者和健康对照尿液样本中的不同蛋白质峰。我们通过UniProt数据库检索蛋白峰对应的蛋白,并利用NIH DAVID数据库鉴定CKD及其并发症的信号通路。通过与健康对照者比较,CKD患者尿液样本中发现了42种低丰度蛋白质和46种高丰度蛋白质。从调节蛋白中鉴定出与 CKD 及其并发症相关的 7 条 KEGG 通路。这些途径包括趋化因子信号传导途径、细胞因子-细胞因子受体相互作用、氧化磷酸化、心肌收缩、阿尔茨海默病、帕金森病和唾液分泌。在 CKD 2、3、4 和 5 阶段,五种蛋白质表现出显着的丰度差异。差异蛋白信号和调控的信号通路将为 CKD 及其并发症的发病机制提供新的见解。这些改变的蛋白质将来还可以作为新的生物标志物,用于通过尿液检测进行 CKD 及其并发症的无创且便捷的诊断方法。

更新日期:2020-11-27
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