Department of Pediatrics, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China.
Department of Hematology and Oncology, Shenzhen Children's Hospital of China Medical University, Shenzhen, China.
Front Immunol. 2022 Oct 21;13:1034821. doi: 10.3389/fimmu.2022.1034821. eCollection 2022.
Acute lung injury (ALI) is the most common complication of sepsis. Intravenous injection of HUMSCs can regulate the level of circulating endothelial cytokines and alleviate lung injury in juvenile septic rats. In this study, we performed proteomic and phosphorylated proteomic analysis of lung tissue of juvenile septic rats after Human Umbilical Cord Mesenchymal Stem Cells (HUMSCs) intervention for the first time, and screened the potential proteins and pathways of HUMSCs for therapeutic effect. The 4D proteome quantitative technique was used to quantitatively analyze the lung tissues of septic rats 24 hours (3 biological samples) and 24 hours after HUMSCs intervention (3 biological samples). A total of 213 proteins were identified as differentially expressed proteins, and 971 phosphorylation sites changed significantly. Based on the public database, we analyzed the functional enrichment of these proteins and phosphorylated proteins. In addition, Tenascin-C may be the key differential protein and ECM receptor interaction pathway may be the main signal pathway by using various algorithms to analyze the protein-protein interaction network. Phosphorylation analysis showed that tight junction pathway was closely related to immune inflammatory reaction, and EGFR interacted most, which may be the key differential phosphorylated protein. Finally, 123 conserved motifs of serine phosphorylation site (pS) and 17 conserved motifs of threonine (pT) phosphorylation sites were identified by motif analysis of phosphorylation sites. Results from proteomics and phosphorylated proteomics, the potential new therapeutic targets of HUMSCs in alleviating lung injury in juvenile septic rats were revealed.
急性肺损伤(ALI)是脓毒症最常见的并发症。静脉注射人脐带来源的间充质干细胞(HUMSCs)可以调节循环内皮细胞因子的水平,减轻幼年脓毒症大鼠的肺损伤。在这项研究中,我们首次对 HUMSCs 干预幼年脓毒症大鼠的肺组织进行了蛋白质组学和磷酸化蛋白质组学分析,筛选了 HUMSCs 治疗作用的潜在蛋白和途径。我们使用 4D 蛋白质组定量技术对脓毒症大鼠肺组织 24 小时(3 个生物学样本)和 HUMSCs 干预 24 小时后(3 个生物学样本)进行了定量分析。共鉴定出 213 个差异表达蛋白,971 个磷酸化位点发生显著变化。基于公共数据库,我们分析了这些蛋白和磷酸化蛋白的功能富集。此外,通过使用各种算法分析蛋白质-蛋白质相互作用网络,我们发现 Tenascin-C 可能是关键的差异蛋白,ECM 受体相互作用途径可能是主要的信号途径。磷酸化分析表明,紧密连接途径与免疫炎症反应密切相关,EGFR 相互作用最多,可能是关键的差异磷酸化蛋白。最后,通过磷酸化位点的基序分析,鉴定出 123 个丝氨酸磷酸化位点(pS)的保守基序和 17 个苏氨酸(pT)磷酸化位点的保守基序。蛋白质组学和磷酸化蛋白质组学的结果揭示了 HUMSCs 缓解幼年脓毒症大鼠肺损伤的潜在新治疗靶点。