系统性红斑狼疮患者外周血单个核细胞的磷蛋白组学和基因网络分析

目的 通过检测系统性红斑狼疮（SLE）患者外周血单个核细胞（PBMCs）的磷蛋白组学分析,为SLE进一步机制研究及治疗奠定基础.方法 使用二氧化钛富集SLE患者15例和15名健康受试者PBMCs的磷酸化肽段,进行质谱分析;然后进行磷酸化肽段和磷酸化位点鉴定,并进行生物信息学分析.结果 SLE患者与正常人存在有差异的1 035个磷酸化位点,与标注蛋白对应的基因有618个.基因网络分析发现,Src、RELA、HDAC1等连接度高,为hub基因,在维持网络的稳定性中起着重要的作用.结论 SLE患者PBMCs具有差异性的磷酸化蛋白质及肽段,异常蛋白磷酸化有助于SLE发病机制的研究;与hub基因可作为机制研究参考和补充,并可作为治疗研究靶点.

Phosphoproteome and gene network analysis in PBMC of SLE patients

Objective To investigate the aberrant expression of phosphoproteome analysis of peripheral blood mononuclear cells （PBMCs） in patients with systemic lupus erythematosus （SLE）.Methods Phosphopeptides were enriched using TiO2 from PBMCs isolated from 15 SLE patients and 15 healthy subjects,then analyzed by automated LC-MS/MS analysis.Phosphorylation sites were identified and quantitated by MASCOT and MaxQuant.Differential expressed proteins and peptides were screened based on the bioinformatics analysis.Results A total of 1 035 phosphorylation sites were identified from SLE compared with normal subjects,618 corresponding genes were screened out in annotation proteins.Gene network analysis showed that rous sarcoma oncogene （Src）,v-rel reticuloendotheliosis viral oncogene homolog A （RELA）,histone deacetylase （HDAC1）,delta （PRKCD） played important roles in the stability of the network.Conclusions Differently phosphorylated proteins and peptides can be detected in patients with SLE.These data suggest that aberrant protein phosphorylation may contribute to SLE pathogenesis,which can be used as a mechanism of reference and supplement combined with hub genes,and might be used as a potential target for treatment and research of SLE.