Background. Although mesenchymal stem cell- (MSC-) derived extracellular vesicles (EVs) are as effective as MSCs in the suppression of allergic airway inflammation, few studies have explored the molecular mechanisms of MSC-derived EVs in allergic airway diseases. The objective of this study was to evaluate differentially expressed genes (DEGs) in the lung associated with the suppression of allergic airway inflammation using adipose stem cell- (ASC-) derived EVs. Methods. C57BL/6 mice were sensitized to ovalbumin (OVA) by intraperitoneal injection and challenged intranasally with OVA. To evaluate the effect of ASC-derived EVs on allergic airway inflammation, 10 μg/50 μL of EVs were administered intranasally prior to OVA challenge. Lung tissues were removed and DEGs were compared pairwise among the three groups. DEG profiles and hierarchical clustering of the identified genes were analyzed to evaluate changes in gene expression. Real-time PCR was performed to determine the expression levels of genes upregulated after treatment with ASC-derived EVs. Enrichment analysis based on the Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were also performed to further identify the function of DEGs. Results. Expression of paraoxonase 1 (PON1), brain-expressed X-linked 2 (Bex2), insulin-like growth factor binding protein 6 (Igfbp6), formyl peptide receptor 1 (Fpr1), and secretoglobin family 1C member 1 (Scgb1c1) was significantly increased in asthmatic mice following treatment with ASC-derived EVs. GO enrichment and KEGG pathway analysis showed that these genes were strongly associated with immune system processes and their regulation, cellular processes, single-organism processes, and biological regulation. Conclusion. These results suggest that the DEGs identified in this study (PON1, Bex2, Igfbp6, Fpr1, and Scgb1c1) may be involved in the amelioration of allergic airway inflammation by ASC-derived EVs.

中文翻译：

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与脂肪干细胞来源的细胞外囊泡抑制过敏性气道炎症相关的肺基因的筛选和功能通路分析。

背景。尽管间充质干细胞 (MSC-) 衍生的细胞外囊泡 (EVs) 在抑制过敏性气道炎症方面与 MSCs 一样有效，但很少有研究探索 MSC 衍生的 EVs 在过敏性气道疾病中的分子机制。本研究的目的是使用脂肪干细胞 (ASC-) 衍生的 EV 评估与抑制过敏性气道炎症相关的肺部差异表达基因 (DEG)。方法。通过腹膜内注射使 C57BL/6 小鼠对卵清蛋白 (OVA) 敏感，并用 OVA 鼻内攻击。为了评估 ASC 衍生的 EVs 对过敏性气道炎症的影响，10  μ g/50  μ在 OVA 攻击之前鼻内施用 L 的 EV。去除肺组织并在三组之间成对比较DEG。分析已识别基因的 DEG 谱和层次聚类以评估基因表达的变化。进行实时 PCR 以确定用 ASC 衍生的 EV 处理后上调的基因的表达水平。还进行了基于基因本体（GO）数据库和京都基因和基因组百科全书（KEGG）通路分析的富集分析，以进一步确定 DEG 的功能。结果. 对氧磷酶 1 (PON1)、脑表达 X-linked 2 (Bex2)、胰岛素样生长因子结合蛋白 6 (Igfbp6)、甲酰肽受体 1 (Fpr1) 和分泌珠蛋白家族 1C 成员 1 (Scgb1c1) 的表达显着哮喘小鼠在用 ASC 衍生的 EV 治疗后增加。GO富集和KEGG通路分析表明，这些基因与免疫系统过程及其调节、细胞过程、单一生物过程和生物调节密切相关。结论。这些结果表明，本研究中鉴定的 DEG（PON1、Bex2、Igfbp6、Fpr1 和 Scgb1c1）可能参与 ASC 衍生的 EV 对过敏性气道炎症的改善。