BACKGROUND The nasal epithelial barrier is the first line of defense against the deep entry of pathogens or aeroallergens and is more critical in allergic rhinitis (AR). Restoring epithelial barrier dysfunction might be a promising strategy for AR. Recent studies reported that mesenchymal stem cell-derived small extracellular vesicles (MSC-sEV) potentially inhibit the inflammation response and promote tissue regeneration. However, their effect on nasal epithelial cells remains unknown. OBJECTIVES This study sought to describe the therapeutic effect of MSC-sEV on AR, particularly focusing their effect on nasal epithelial cells and underlying molecular mechanisms. METHODS We utilized an ovalbumin-induced mouse model to study AR. Both primary and immortalized human nasal epithelial cells (HNEpC) were used to further validate the therapeutic effects of MSC-sEV on epithelial cell function. Then we constructed microRNA (miR)-143 overexpressing and low-expressing HNEpC and MSC-sEV to elucidate molecular mechanisms. Transcriptome analysis was performed to identify the downstream pathways involved. RESULTS MSC-sEV successfully maintained nasal barrier integrity in AR mouse model. The MSC-sEV therapeutic effect on the nasal barrier was substantiated in HNEpC. Mechanistically, miR-143 was a candidate mediator of the above effects. Subsequently, transfecting HNEpC with miR-143 partially mimicked the restoring effect of MSC-sEV. MSC-sEV overexpressing miR-143 exerted more therapeutic effects on tight junctions and barrier integrity. Moreover, miR-143 regulated the glycogen synthase kinase-3β (GSK3B) pathway. CONCLUSIONS Our results indicated that MSC-sEV mitigated AR and restored nasal epithelial barrier dysfunction through the miR-143-GSK3B axis, which suggested that MSC-sEV have the remarkable ability to treat AR.

中文翻译：

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间充质干细胞来源的细胞外小囊泡通过人鼻上皮细胞中的 miR-143-GSK3B 恢复过敏性鼻炎的鼻屏障功能。


背景 鼻上皮屏障是抵御病原体或气源过敏原深入的第一道防线，在过敏性鼻炎 （AR） 中更为关键。恢复上皮屏障功能障碍可能是 AR 的一个有前途的策略。最近的研究报道，间充质干细胞衍生的小细胞外囊泡 （MSC-sEV） 可能抑制炎症反应并促进组织再生。然而，它们对鼻上皮细胞的影响仍然未知。目的 本研究试图描述 MSC-sEV 对 AR 的治疗效果，特别是关注它们对鼻上皮细胞的影响和潜在的分子机制。方法 我们利用卵清蛋白诱导的小鼠模型来研究 AR。原代和永生化人鼻上皮细胞 （HNEpC） 均用于进一步验证 MSC-sEV 对上皮细胞功能的治疗作用。然后我们构建了过表达和低表达 HNEpC 和 MSC-sEV 的 microRNA （miR）-143 来阐明分子机制。进行转录组分析以确定所涉及的下游途径。结果 MSC-sEV 在 AR 小鼠模型中成功维持了鼻屏障的完整性。MSC-sEV 对鼻屏障的治疗作用在 HNEpC 中得到证实。从机制上讲，miR-143 是上述作用的候选介质。随后，用 miR-143 转染 HNEpC 部分模拟了 MSC-sEV 的恢复作用。过表达 miR-143 的 MSC-sEV 对紧密连接和屏障完整性产生了更多的治疗作用。此外，miR-143 调节糖原合成酶激酶-3β （GSK3B） 通路。 结论 我们的结果表明，MSC-sEV 通过 miR-143-GSK3B 轴减轻 AR 并恢复鼻上皮屏障功能障碍，这表明 MSC-sEV 具有显着的治疗 AR 的能力。