系统性红斑狼疮外周血单个核细胞磷酸化蛋白质组学研究

The phosphoproteome analysis in PBMCs of SLE patients

目的通过系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMCs)的磷蛋白组学分析,为SLE的进一步机制研究及治疗奠定基础。方法收集15例SLE患者和15例健康受试者的外周血,使用TiO2富集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。共筛选出12条代谢通路,其中丝裂原活化蛋白激酶(MAPKs)通路含差异的磷酸化位点最多。结论 SLE患者PBMCs具有差异的磷酸化蛋白质及肽段,与代谢通路一起可作为SLE发病机制研究参考和补充,并可作为治疗靶点研究。

Objective To investigate the aberrant expression of phosphoproteome analysis of peripheral blood mononuclear cells（ PBMCs） in patients with systemic lupus erythematosus（ SLE） . Lay the foundation for further research of mechanism and treatment in patients with SLE. Methods Phosphopeptides were enriched using TiO2 from PBMCs of patients and 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 1 035 phosphorylation sites were identified from SLE comprared with normal subjects, 618 corresponding genes were screened out in annotation proteins. Pathway analyses showed 12 signaling pathways were identified. There were the most difference phosphorylation sites in mitogen activated protein kinases（ MAPK） signaling pathway. Conclusion Differently phosphorylated proteins and peptides can be detected in patients with SLE, which can be used as a mechanism of reference and supplement combined with metabolic pathway, and might be used as a potential target for treatment and research of SLE.