Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Aging (Albany NY). 2020 Jul 26;12(14):14966-14977. doi: 10.18632/aging.103555.
Intestinal barrier dysfunction is a hallmark of inflammatory bowel disease (IBD). MiR-155 is increased in colitis and downregulates expression of hypoxia-inducible factor 1α (HIF-1α). Here, we investigated the effects of miR-155 on intestinal barrier dysfunction in dextran sulfate sodium (DSS)-induced colitis. We found that miR-155 antagomir treatment relieved weight loss and intestinal damage in IBD mouse models (P < 0.05). Furthermore, electron microscopy and immunofluorescence imaging showed that miR-155 increased intestinal barrier dysfunction and downregulated the expression of tight junction proteins in DSS-induced colitis. FG-4497, which upregulates HIF-1α expression, elicited protective effects on the intestinal barrier in DSS-induced colitis. Dual luciferase reporter assays also confirmed that miR-155 downregulated expression of HIF-1α. Finally, we discovered that HIF-1α levels were elevated by miR-155 antagomir treatment (P < 0.05) and that TFF-3 expression correlated positively with HIF-1α expression. These results suggest that miR-155 contributes to DSS-induced colitis by promoting intestinal barrier dysfunction and inhibiting the HIF-1α/TFF-3 axis.
肠道屏障功能障碍是炎症性肠病（IBD）的一个标志。miR-155 在结肠炎中增加，并下调缺氧诱导因子 1α（HIF-1α）的表达。在这里，我们研究了 miR-155 对葡聚糖硫酸钠（DSS）诱导的结肠炎中肠道屏障功能障碍的影响。我们发现 miR-155 反义寡核苷酸治疗减轻了 IBD 小鼠模型的体重减轻和肠道损伤（P<0.05）。此外，电子显微镜和免疫荧光成像显示，miR-155 增加了肠道屏障功能障碍，并下调了 DSS 诱导的结肠炎中紧密连接蛋白的表达。上调 HIF-1α 表达的 FG-4497 对 DSS 诱导的结肠炎中的肠道屏障具有保护作用。双荧光素酶报告基因检测也证实了 miR-155 下调了 HIF-1α 的表达。最后，我们发现 miR-155 反义寡核苷酸治疗可上调 HIF-1α 水平（P<0.05），TFF-3 的表达与 HIF-1α 的表达呈正相关。这些结果表明，miR-155 通过促进肠道屏障功能障碍和抑制 HIF-1α/TFF-3 轴来促进 DSS 诱导的结肠炎。
