Proteomic analysis of hucMSCs in lipopolysaccharide-induced ALI mice

Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by a high mortality rate, and its treatment is relatively straightforward. The application of human umbilical cord mesenchymal stem cells (hucMSCs) for the treatment of ARDS has emerged as a novel therapeutic approach and has been the subject of extensive research. In this study, a mouse model of acute lung injury (ALI) was established, and hucMSCs were administered via tail vein injection to investigate the pathogenesis of ARDS and the protein alterations following hucMSC treatment. Data-independent acquisition (DIA) was employed for the proteomic analysis of lung tissue, which included the identification of differentially expressed proteins (DEPs) and their associated pathways. The relevant DEPs identified in the lung tissues of the three groups of mice included Arid5a, Mrpl4, Cxcl12, and Rnf121. Notably, silencing the expression of Cxcl12 in hucMSCs significantly inhibited the therapeutic effect of these cells. Additionally, the signaling pathways associated with the relevant DEPs were analyzed. The DEPs and the enriched pathways discussed herein provide valuable insights into the pathogenesis of ARDS and the potential applications of hucMSCs急性呼吸窘迫综合征（Acute respiratory distress syndrome, ARDS）是一类以高病死率为特征的临床综合征，其治疗方案相对明确。将人脐带间充质干细胞（human umbilical cord mesenchymal stem cells, hucMSCs）用于治疗ARDS已成为新兴治疗策略，并得到了广泛研究。本研究构建了急性肺损伤（acute lung injury, ALI）小鼠模型，通过尾静脉注射人脐带间充质干细胞，以探究ARDS的发病机制以及人脐带间充质干细胞干预后的蛋白表达变化。本研究采用数据非依赖采集（Data-independent acquisition, DIA）技术对肺组织进行蛋白质组学分析，涵盖差异表达蛋白（differentially expressed proteins, DEPs）的鉴定及其相关通路分析。三组小鼠肺组织中鉴定出的差异表达蛋白包括Arid5a、Mrpl4、Cxcl12及Rnf121。值得注意的是，在人脐带间充质干细胞中沉默Cxcl12的表达可显著抑制其治疗效应。此外，本研究还对上述差异表达蛋白所关联的信号通路进行了解析。本研究获得的差异表达蛋白及其富集通路可为ARDS的发病机制研究及人脐带间充质干细胞的潜在应用提供宝贵的理论参考。