Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Tiantan Xili the 6th, Dongcheng District, Beijing, 100050, China.
Sci Rep. 2019 Apr 5;9(1):5747. doi: 10.1038/s41598-019-42287-7.
New diagnostic biomarkers or therapeutic targets for sepsis have substantial significance for critical care medicine. In this study, 192 differentially expressed proteins were selected through iTRAQ. Based on cluster analysis of protein expression dynamics and protein-protein interactions, hemopexin, vimentin, and heat shock protein 90 were selected for further investigation. It was demonstrated that serum vimentin (VIM) levels were significantly increased in patients with sepsis and septic shock compared to controls and that VIM expression was significantly increased in lymphocytes isolated from septic shock and sepsis patients compared to controls. Moreover, a nonsurvivor group had higher serum VIM levels and VIM expression in lymphocytes. Caspase-3 was significantly upregulated in Jurkat T cells lacking VIM and when exposed to LPS compared to control cells. In contrast, caspase-3 was reduced nearly 40% in cells over-expressing VIM. IL-2, IL-10 and IFN-α levels were significantly decreased in cells lacking VIM compared to control cells, whereas they were not significantly altered in cells over-expressing VIM. These findings suggest that VIM modulates lymphocyte apoptosis and inflammatory responses and that VIM could be a new target for the diagnosis and prognostic prediction of patients with sepsis or septic shock.
用于脓毒症的新诊断生物标志物或治疗靶点对重症医学具有重要意义。在这项研究中，通过 iTRAQ 选择了 192 个差异表达蛋白。基于蛋白表达动力学和蛋白-蛋白相互作用的聚类分析，选择了触珠蛋白、波形蛋白和热休克蛋白 90 进行进一步研究。结果表明，与对照组相比，脓毒症和感染性休克患者的血清波形蛋白（VIM）水平显著升高，且从感染性休克和脓毒症患者分离的淋巴细胞中 VIM 表达显著升高。此外，非幸存者组的血清 VIM 水平和淋巴细胞中 VIM 表达更高。与对照细胞相比，缺乏 VIM 的 Jurkat T 细胞和暴露于 LPS 时 caspase-3 显著上调。相比之下，过表达 VIM 的细胞中 caspase-3 减少了近 40%。与对照细胞相比，缺乏 VIM 的细胞中 IL-2、IL-10 和 IFN-α 水平显著降低，而过表达 VIM 的细胞中这些水平没有显著改变。这些发现表明，VIM 调节淋巴细胞凋亡和炎症反应，VIM 可能成为脓毒症或感染性休克患者诊断和预后预测的新靶点。
