National Institute of Gastroenterology “S. de Bellis”, IRCCS Research Hospital, 70013 Castellana Grotte, Bari, Italy.
Int J Mol Sci. 2022 May 23;23(10):5840. doi: 10.3390/ijms23105840.
Defects in the intestinal epithelial barrier functions characterize inflammatory conditions such as Inflammatory Bowel Disease (IBD). Overexpression of pro-inflammatory cytokines such as TNF-α, IL-1B, IL-6 and INF-γ trigger epithelial damage. These cytokines are due to upregulation of claudin-2 (CLDN2) that form a pore channel, resulting in redistribution of TJs and an alteration of barrier permeability. Recently, we demonstrated that miR-195-5p is able to regulate CLDN2 and indirectly also CLDN1 in intestinal epithelial cells. Now, we aimed to investigate the modulation of miR-195-5p on the expression of CLDN2 and other TJs under inflammatory conditions induced by TNF-α. We demonstrated that miR-195-5p also modulated the expression of CLDN2 levels after stimulation with TNF-α. In addition, we discovered the role of miR-195-5p in the integrity of the intestinal barrier and in promoting the restoration of the intestinal epithelial. Moreover, we established that replacement of miR-195-5p attenuated the colonic inflammatory response in DSS-induced, colitis and it reduced colonic permeability. In conclusion, our data revealed the role of miR-195-5p in intestinal inflammation in ulcerative colitis, suggesting a potential pharmacological target for new therapeutic approaches.
肠上皮屏障功能缺陷是炎症性疾病的特征，如炎症性肠病（IBD）。促炎细胞因子如 TNF-α、IL-1B、IL-6 和 INF-γ的过度表达会触发上皮损伤。这些细胞因子是由于 Claudin-2（CLDN2）的上调而形成孔道，导致 TJ 重新分布和屏障通透性改变。最近，我们证明了 miR-195-5p 能够调节肠上皮细胞中的 CLDN2，并间接地调节 CLDN1。现在，我们旨在研究 miR-195-5p 在 TNF-α诱导的炎症条件下对 CLDN2 和其他 TJ 的表达的调节作用。我们证明了 miR-195-5p 也可以调节 TNF-α刺激后 CLDN2 水平的表达。此外，我们发现了 miR-195-5p 在肠屏障完整性和促进肠上皮修复中的作用。此外，我们确定了 miR-195-5p 的替代可以减轻 DSS 诱导的结肠炎中的结肠炎症反应，并降低结肠通透性。总之，我们的数据揭示了 miR-195-5p 在溃疡性结肠炎中的肠炎症中的作用，为新的治疗方法提供了潜在的药理靶点。
