Inhibition of lncRNA NEAT1 suppresses the inflammatory response in IBD by modulating the intestinal epithelial barrier and by exosome-mediated polarization of macrophages
Inhibition of lncRNA NEAT1 suppresses the inflammatory response in IBD by modulating the intestinal epithelial barrier and by exosome-mediated polarization of macrophages
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DOI：
10.3892/ijmm.2018.3829
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发表时间：
2018-11-01
影响因子：
5.4
通讯作者：
Shen, Shourong
中科院分区：
文献类型：
--
作者：
Liu, Rui;Tang, Anliu;Shen, Shourong
炎症性肠病（IBD）是一种多因子炎症性疾病，越来越多的证据表明IBD的发病机制与肠上皮屏障损伤有关。长链非编码rna （Long non-coding RNAs, lncRNAs）是一类全长约200个核苷酸的转录本，具有有限的蛋白质编码能力。核副斑装配转录本1 （NEAT1）是最近发现的一种核限制性lncRNA，定位于亚核结构，称为副斑，并以多种方式参与免疫反应。然而，NEAT1在IBD中的功能尚未完全阐明。本研究采用逆转录-定量聚合酶链反应法测定NEAT1 lncRNA在IBD血清样本和组织中的表达水平。此外，通过测定跨上皮电阻以及western blot和免疫荧光分析，研究了NEAT1对结肠细胞通透性的影响。此外，通过葡聚糖硫酸钠法研究NEAT1下调对小鼠IBD的影响。本研究通过检测NEAT1在IBD细胞和动物模型中的表达水平，研究抑制NEAT1表达后肠上皮细胞通透性的变化。此外，研究了不同处理后上皮细胞和巨噬细胞的表型转化。结果提示NEAT1在IBD中高表达，并通过调节肠上皮屏障和外泌体介导的巨噬细胞极化参与炎症反应。NEAT1的下调通过调节肠上皮屏障和外泌体介导的巨噬细胞极化抑制炎症反应。本研究的结果揭示了靶向NEAT1治疗IBD的潜在策略。
Inflammatory bowel disease (IBD) is a multifactorial inflammatory disease, and increasing evidence has demonstrated that the mechanism of the pathogenesis of IBD is associated with intestinal epithelial barrier injury. Long non-coding RNAs (lncRNAs) are a class of transcripts >200 nucleotides in length with limited protein-coding capability. Nuclear paraspeckle assembly transcript 1 (NEAT1) is a recently identified nuclear-restricted lncRNA, which localizes in subnuclear structures, termed paraspeckles, and is involved in the immune response in a variety of ways. However, the function of NEAT1 in IBD remains to be fully elucidated. In the present study, reverse transcription-quantitative polymerase chain reaction assays were performed to determine the expression levels of NEAT1 lncRNA in IBD serum samples and tissues. Furthermore, the effect of NEAT1 on the cell permeability of colon cells was investigated via determination of trans-epithelial electrical resistance as well as performance of western blot and immunofluorescence assays. In addition, dextran sodium sulfate assays were performed to investigate the effect of downregulation of NEAT1 in IBD of mice. The present study detected the expression levels of NEAT1 in IBD cells and animal models to examine the changes in intestinal epithelial cell permeability following inhibition of the expression of NEAT1. In addition, phenotypic transformation was examined following different treatments in epithelial cells and macrophages. The results suggested that the expression of NEAT1 was high in IBD and was involved in the inflammatory response by regulating the intestinal epithelial barrier and through exosome-mediated polarization of macrophages. The downregulation of NEAT1 suppressed the inflammatory response by modulating the intestinal epithelial barrier and through exosome-mediated polarization of macrophages in IBD. The results of the present study revealed a potential strategy of targeting NEAT1 for IBD therapy.