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整合的泪液蛋白质组和代谢组学通过干眼综合征关键调控通路揭示炎症相关分子谱。

Integrated Tear Proteome and Metabolome Reveal Panels of Inflammatory-Related Molecules via Key Regulatory Pathways in Dry Eye Syndrome.

机构信息

Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College , Fudan University , Shanghai , China.

Jiangxi Provincial Key Laboratory of Translational Medicine and Oncology , Jiangxi Cancer Hospital, Jiangxi Cancer Center , Nanchang , 330029 , People's Republic of China.

出版信息

J Proteome Res. 2019 May 3;18(5):2321-2330. doi: 10.1021/acs.jproteome.9b00149. Epub 2019 Apr 16.

Abstract

Dry eye syndrome (DES) is a growing public health concern with a high global prevalence; however, the fundamental processes involved in its pathogenic mechanisms remain poorly understood. In the present study, we applied nanoscale liquid chromatography and quadrupole time-of-flight tandem mass spectrometry (nanoLC/Q-TOF-MS/MS) and ultraperformance LC/Q-TOF-MS/MS technologies on tear samples obtained from 18 dry eye patients and 19 healthy controls for integrated proteomic and metabolomic analyses. Overall, 1031 tear proteins were detected, while 190 proteins were determined to be significantly expressed in dry eye patients. Further functional analysis suggested that various biological processes were highly expressed and involved in the pathogenesis of DES, especially immune and inflammatory processes. In total, 156 named metabolites were identified, among which 34 were found to be significantly changed in dry eye patients. The results highlighted the key elements, especially inflammatory-related proteins and metabolites that played important roles in the development of DES. Further, the regulatory roles of primary pathways, including complement and coagulation cascades, glycolysis/gluconeogenesis, and amino acid metabolism, were also identified as processes involved in DES. Collectively, our work not only provided insight into the potential biomarkers of DES for diagnostic and prognostic purposes but extended our knowledge of the physiopathology of this syndrome.

摘要

干眼症(DES)是一个日益受到关注的公共卫生问题,具有很高的全球患病率;然而,其发病机制涉及的基本过程仍知之甚少。在本研究中,我们应用纳升级液相色谱和四极杆飞行时间串联质谱(nanoLC/Q-TOF-MS/MS)和超高效液相色谱和四极杆飞行时间串联质谱(UPLC/Q-TOF-MS/MS)技术对 18 例干眼症患者和 19 例健康对照者的泪液样本进行了综合蛋白质组学和代谢组学分析。总的来说,检测到了 1031 种泪液蛋白,而在干眼症患者中,有 190 种蛋白被确定为显著表达。进一步的功能分析表明,各种生物学过程被高度表达,并参与了 DES 的发病机制,特别是免疫和炎症过程。总共鉴定出 156 种命名代谢物,其中 34 种在干眼症患者中明显改变。结果强调了关键要素,特别是炎症相关蛋白和代谢物,它们在 DES 的发展中发挥了重要作用。此外,还确定了包括补体和凝血级联、糖酵解/糖异生和氨基酸代谢在内的主要途径的调节作用,这些途径是 DES 涉及的过程。总之,我们的工作不仅为 DES 的诊断和预后提供了潜在的生物标志物,还扩展了我们对该综合征病理生理学的认识。

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