MiR-375 is downregulated in epithelial cells after IL-13 stimulation and regulates an IL-13-induced epithelial transcriptome.
MiR-375 is downregulated in epithelial cells after IL-13 stimulation and regulates an IL-13-induced epithelial transcriptome.
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IL-13 刺激后，MiR-375 在上皮细胞中下调，并调节 IL-13 诱导的上皮转录组。
作者：
IL-13诱导的上皮基因和蛋白表达变化是多种过敏性疾病发病机制的核心。在此，我们使用人食管鳞状上皮细胞和支气管柱状上皮细胞，鉴定出在 IL-13 刺激后受到差异调节的 miRNA。在 IL-13 调节的 miRNA 中，miR-375 显示出保守的下调模式。此外，IL-13肺转基因小鼠的肺中miR-375下调。随后，我们分析了一种以 IL-13 过量产生为特征的人类疾病——过敏性疾病嗜酸粒细胞性食管炎 (EE) 中的 miR-375 水平，并观察到与对照患者相比，EE 患者样本中 miR-375 的下调。 MiR-375 表达水平反映了疾病活动性，随着缓解而正常化，并且与过敏性炎症的程度呈负相关。使用慢病毒策略和上皮细胞中的全转录组分析，miR-375过表达足以在体外显着改变上皮细胞中IL-13相关的免疫炎症通路，进一步证实了miR-375和IL-13之间的相互作用。总而言之，我们的结果支持 miRNA（尤其是 miR-375）在调节和微调 IL-13 介导的反应中的关键作用。
IL-13-induced epithelial gene and protein expression changes are central to the pathogenesis of multiple allergic diseases. Herein, using human esophageal squamous and bronchial columnar epithelial cells, we identified miRNAs that were differentially regulated after IL-13 stimulation. Among the IL-13-regulated miRNAs, miR-375 showed a conserved pattern of down-regulation. Furthermore, miR-375 was down regulated in the lung of IL-13 lung transgenic mice. We subsequently analyzed miR-375 levels in a human disease characterized by IL-13 overproduction – the allergic disorder eosinophilic esophagitis (EE), and observed down-regulation of miR-375 in EE patient samples compared to control patients. MiR-375 expression levels reflected disease activity, normalized with remission, and inversely correlated to the degree of allergic inflammation. Using a lentiviral strategy and whole-transcriptome analysis in epithelial cells, miR-375 over-expression was sufficient to markedly modify IL-13-associated immunoinflammatory pathways in epithelial cells in vitro, further substantiating interactions between miR-375 and IL-13. Taken together, our results support a key role of miRNAs, particularly miR-375, in regulating and fine-tuning IL-13 mediated responses.