Huo Shuai, Wang Hongxin, Yan Meixia, Xu Peng, Song Tingting, Li Chuang, Tian Ruimin, Chen Xiaoling, Bao Kun, Xie Ying, Xu Ping, Zhu Weimin, Liu Fengsong, Mao Wei, Shao Chen
State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China.
The Second Clinical Medical College, Guangzhou University of Chinese Medicine,Guangzhou 510405, China.
ACS Omega. 2021 Mar 29;6(14):9500-9508. doi: 10.1021/acsomega.0c06229. eCollection 2021 Apr 13.
Hyperuricemia (HUA), a chronic disease caused by metabolic disorders of purine, is often accompanied by other diseases such as gout, type 2 diabetes mellitus (T2DM), and hyperlipidemia. However, little is known about the relationship between HUA and these diseases on the protein level. We performed label-free liquid chromatography MS/MS spectrometry analysis of urine samples from 26 HUA patients and 25 healthy controls, attempting to establish the possible protein links between HUA and these diseases by profiling urine proteome. A total of 2119 proteins were characterized in sample proteomes. Among them, 11 were found decreased and 2 were found increased in HUA samples. Plausible pathways found by enrichment analysis of these differentially expressed proteins (DEPs) include the processes for insulin receptor recycling and lipid metabolism, suggesting potential links between HUA and T2DM and hyperlipidemia. The abundance changes of three key proteins (VATB1, CFAD, and APOC3) involved in these processes were validated by enzyme-linked immunosorbent assay (ELISA). In conclusion, our result provides proteomic evidence, for the first time, that the aberrant pathways enriched by described key DEPs are closely related to the incidence of HUA and its concomitant diseases.
高尿酸血症（HUA）是一种由嘌呤代谢紊乱引起的慢性疾病，常伴有痛风、2型糖尿病（T2DM）和高脂血症等其他疾病。然而，在蛋白质水平上，关于HUA与这些疾病之间的关系知之甚少。我们对26例HUA患者和25例健康对照者的尿液样本进行了无标记液相色谱串联质谱分析，试图通过分析尿液蛋白质组来建立HUA与这些疾病之间可能的蛋白质联系。在样本蛋白质组中共鉴定出2119种蛋白质。其中，在HUA样本中发现11种蛋白质减少，2种蛋白质增加。通过对这些差异表达蛋白（DEPs）的富集分析发现的合理途径包括胰岛素受体再循环和脂质代谢过程，提示HUA与T2DM和高脂血症之间存在潜在联系。通过酶联免疫吸附测定（ELISA）验证了参与这些过程的三种关键蛋白（VATB1、CFAD和APOC3）的丰度变化。总之，我们的结果首次提供了蛋白质组学证据，表明所述关键DEPs富集的异常途径与HUA及其伴发疾病的发生密切相关。
