Growing evidence suggested that microRNAs (miRNAs) contributed to the progression of Crohn’s disease (CD), but the exact physiological functions of many miRNAs in CD patients still remain illusive. In this study, we explore the potent pathogenicity of miRNAs in CD. Expressions of miRNAs and aryl hydrocarbon receptor (AHR) protein were determined in the colitic colon of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis mice and CD patients. Colitis was induced in wild-type (WT), miR-124a overexpression (miR-124a-Nju), and AHR knockout (AHR^−/−) mice. Intestinal barrier function was evaluated in colitis mice and Caco2 monolayers. There was a negative relationship between miR-124a and AHR protein in inflamed colons from CD patients. MiR-124a-Nju and AHR^−/− mice treated with TNBS had more severe intestinal inflammation than WT mice. Both miR-124a-Nju mice and AHR^−/− mice underwent evident intestinal barrier destruction, and anti-miR-124a administration could reverse this dysfunction in miR-124a-Nju mice but not in AHR^−/− mice. In vitro studies revealed that miR-124a mimics downregulated the expression of AHR and tight junction proteins and induced hyperpermeability by increasing miR-124a expression, which was abrogated by miR-124a inhibitor and AHR antagonist FICZ. This study suggests that miR-124a can induce intestinal inflammation and cause intestinal barrier dysfunction by supressing AHR.

越来越多的证据表明，microRNA（miRNA）促进了克罗恩病（CD）的发展，但是CD患者中许多miRNA的确切生理功能仍然仍然不理想。在这项研究中，我们探讨了CD中miRNA的潜在致病性。在2,4,6-三硝基苯磺酸（TNBS）诱导的结肠炎小鼠和CD患者的大肠结肠中确定了miRNA和芳烃受体（AHR）蛋白的表达。在野生型（WT），miR-124a过表达（miR-124a-Nju）和AHR敲除（AHR ^-/-）小鼠中诱发结肠炎。在结肠炎小鼠和Caco2单层中评估肠屏障功能。CD患者发炎的结肠中miR-124a与AHR蛋白之间呈负相关。MiR-124a-Nju和AHR ^-/-TNBS处理的小鼠比WT小鼠的肠道炎症更严重。miR-124a-Nju小鼠和AHR ^-/-小鼠均经历了明显的肠屏障破坏，抗miR-124a的给药可以逆转miR-124a-Nju小鼠的这种功能障碍，但不能逆转AHR ^-/-小鼠的功能障碍。体外研究表明，miR-124a模拟物下调了AHR和紧密连接蛋白的表达，并通过增加miR-124a的表达来诱导通透性过高，而miR-124a抑制剂和AHR拮抗剂FICZ废除了该功能。这项研究表明，miR-124a可以通过抑制AHR来诱导肠道炎症并引起肠道屏障功能障碍。