Department of Huzhou Central Hospital, Affiliated Huzhou Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Institute of Genetics, Zhejiang University School of Medicine, Hangzhou, China.
Front Immunol. 2022 Oct 20;13:1021102. doi: 10.3389/fimmu.2022.1021102. eCollection 2022.
Acute lung injury (ALI) is significantly associated with morbidity and mortality in patients with critical diseases. In recent years, studies have identified that mesenchymal stem/stromal cells (MSCs) ameliorate ALI and pulmonary fibrosis. However, the mechanism underlying this outcome in ALI has not yet been investigated. In this study, RNA sequencing technology was used to analyze the gene expression profile of lung tissue in lipopolysaccharide (LPS)-induced ALI rats following treatment with human umbilical cord MSC (HUCMSC). Differential expression analyses, gene ontology annotation, Kyoto Encyclopedia of Genes and Genomes enrichment, protein-protein interaction network identification, and hub gene analysis were also performed. HUCMSC treatment decreased inflammatory factor production and alveolar exudates, and attenuated lung damage in LPS-induced ALI rats. The RNA-Seq data indicated that HUCMSC treatment activated the IL-17, JAK-STAT, NF-κB, and TNF-α signaling pathways, increased oxygen transport, and decreased extracellular matrix organization. HUCMSC exert beneficial effects on ALI these signaling pathways by reducing inflammation, inhibiting pulmonary fibrosis, and improving lung ventilation. Moreover, our study further revealed the hub genes (, , and ) and signaling pathways involved in HUCMSC treatment, thus providing novel perspectives for future research into the molecular mechanisms underlying cell treatment of ALI. HUCMSC can regulate multiple genes and signaling pathways, which can prevent LPS-induced lung damage in an ALI rat model.
急性肺损伤 (ALI) 与危重病患者的发病率和死亡率显著相关。近年来,研究表明间充质干细胞 (MSCs) 可改善 ALI 和肺纤维化。然而,ALI 中这种结果的机制尚未得到研究。在这项研究中,使用 RNA 测序技术分析了脂多糖 (LPS) 诱导的 ALI 大鼠肺组织在人脐带 MSC (HUCMSC) 治疗后的基因表达谱。还进行了差异表达分析、基因本体注释、京都基因与基因组百科全书富集、蛋白质-蛋白质相互作用网络识别和枢纽基因分析。HUCMSC 治疗可降低 LPS 诱导的 ALI 大鼠中炎症因子的产生和肺泡渗出物,并减轻肺损伤。RNA-Seq 数据表明 HUCMSC 治疗激活了 IL-17、JAK-STAT、NF-κB 和 TNF-α 信号通路,增加了氧气运输,减少了细胞外基质的组织。HUCMSC 通过减少炎症、抑制肺纤维化和改善肺通气对 ALI 发挥有益作用。此外,我们的研究进一步揭示了 HUCMSC 治疗涉及的枢纽基因(、和)和信号通路,从而为细胞治疗 ALI 的分子机制的未来研究提供了新的视角。HUCMSC 可以调节多个基因和信号通路,从而防止 LPS 诱导的 ALI 大鼠模型中的肺损伤。