Aim. Irritable bowel syndrome (IBS) is a multifactorial functional bowel disorder characterized by disruption of the intestinal barrier. Circulating exosomal microRNAs (miRNAs) are involved in regulating epithelial barrier function, and upregulation of miR-148b-5p has been detected in IBS. However, whether exosomal miR-148-5p is involved in the IBS pathogenesis remains unclear. This study was aimed at investigating the relationship of exosomal miR-148-5p with colonic epithelial permeability. Methods. Exosomes were isolated from the serum of IBS patients and healthy controls. HT-29 cells were cultured with the IBS-derived serum exosomes (IBS-exo). Exosome uptake assay was used to evaluate whether the IBS-exo could be absorbed by HT-29 cells. FITC-Dextran flux and transepithelial/endothelial electrical resistance were measured to evaluate epithelial permeability. A luciferase reporter assay was used to determine whether the regulator of G protein signaling- (RGS-) 2 is a target gene of miR-148b-5p. Results. miR-148b-5p was obviously elevated in the IBS-exo compared to the control-exo. Upregulation of miR-148b-5p was observed in the HT-29 cells cultured with IBS-exo. Exposure to IBS-exo increased cell permeability and decreased RGS2 expression. The IBS-exo-induced alterations were obviously reversed by interfering with the miR-148b-5p expression. Mimicking the IBS-exo treatment, miR-148b-5p overexpression increased cell permeability and downregulated RGS2 expression, which were abrogated by overexpressing RGS2. The luciferase reporter assay revealed that RGS2 was a direct target of miR-148b-5p. Conclusions. Serum-derived exosomes from IBS patients increase colonic epithelial permeability via miR-148b-5p/RGS2 signaling.

中文翻译：

---

源自肠易激综合征患者的血清外泌体通过调节人结肠上皮细胞中的 miR-148b-5p/RGS2 信号传导增加细胞通透性

瞄准。肠易激综合征（IBS）是一种多因素的功能性肠道疾病，其特征是肠道屏障的破坏。循环外泌体 microRNA (miRNA) 参与调节上皮屏障功能，并且在 IBS 中检测到 miR-148b-5p 的上调。然而，外泌体 miR-148-5p 是否参与 IBS 发病机制仍不清楚。本研究旨在调查外泌体 miR-148-5p 与结肠上皮通透性的关系。方法. 从 IBS 患者和健康对照的血清中分离出外泌体。HT-29 细胞与 IBS 衍生的血清外泌体 (IBS-exo) 一起培养。外泌体摄取试验用于评估 IBS-exo 是否可以被 HT-29 细胞吸收。测量 FITC-葡聚糖通量和跨上皮/内皮电阻以评估上皮通透性。使用荧光素酶报告基因测定来确定 G 蛋白信号转导调节因子 (RGS-) 2 是否是 miR-148b-5p 的靶基因。结果. 与对照-exo 相比，IBS-exo 中的 miR-148b-5p 明显升高。在用 IBS-exo 培养的 HT-29 细胞中观察到 miR-148b-5p 的上调。暴露于 IBS-exo 会增加细胞通透性并降低 RGS2 表达。通过干扰 miR-148b-5p 表达，IBS-exo 诱导的改变明显逆转。模仿 IBS-exo 治疗，miR-148b-5p 过表达增加细胞通透性并下调 RGS2 表达，这些通过过表达 RGS2 消除。荧光素酶报告基因分析显示 RGS2 是 miR-148b-5p 的直接靶标。结论。来自 IBS 患者的血清衍生外泌体通过 miR-148b-5p/RGS2 信号传导增加结肠上皮通透性。