MiR-155 contributes to intestinal barrier dysfunction in DSS-induced mice colitis via targeting HIF-1α/TFF-3 axis
MiR-155 contributes to intestinal barrier dysfunction in DSS-induced mice colitis via targeting HIF-1α/TFF-3 axis
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MiR-155 通过靶向 HIF-1α/TFF-3 轴导致 DSS 诱导的小鼠结肠炎肠道屏障功能障碍
DOI：
10.18632/aging.103555
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发表时间：
2020-07-31
期刊：
影响因子：
5.2
通讯作者：
Zhu, Xiwen
中科院分区：
文献类型：
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作者：
Liu, Yujin;Zhu, Feng;Zhu, Xiwen
肠屏障功能障碍是炎症性肠病（IBD）的标志。miR-155在结肠炎中增加并下调缺氧诱导因子1 α（HIF-1 α）的表达。在这里，我们研究了miR-155对葡聚糖硫酸钠（DSS）诱导的结肠炎中肠屏障功能障碍的影响。我们发现miR-155治疗减轻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DSS诱导的结肠炎中肠屏障功能障碍，并下调了紧密连接蛋白的表达。FG-4497可上调HIF-1 α表达，对DSS诱导的结肠炎的肠屏障具有保护作用。双荧光素酶报告基因检测也证实了miR-155下调HIF-1 α的表达。最后，我们发现miR-155处理后HIF-1 α水平升高（P < 0.05），TFF-3表达与HIF-1 α表达呈正相关。这些结果表明，miR-155通过促进肠屏障功能障碍和抑制HIF-1 α/TFF-3轴而促成DSS诱导的结肠炎。
Intestinal barrier dysfunction is a hallmark of inflammatory bowel disease (IBD). MiR-155 is increased in colitis and downregulates expression of hypoxia-inducible factor 1 alpha (HIF-1 alpha). 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-1 alpha 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-1 alpha. Finally, we discovered that HIF-1 alpha levels were elevated by miR-155 antagomir treatment (P < 0.05) and that TFF-3 expression correlated positively with HIF-1 alpha expression. These results suggest that miR-155 contributes to DSS-induced colitis by promoting intestinal barrier dysfunction and inhibiting the HIF-1 alpha/TFF-3 axis.