Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
Int J Mol Med. 2018 Nov;42(5):2903-2913. doi: 10.3892/ijmm.2018.3829. Epub 2018 Aug 17.
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.
炎症性肠病（IBD）是一种多因素炎症性疾病，越来越多的证据表明，IBD 的发病机制与肠道上皮屏障损伤有关。长链非编码 RNA（lncRNA）是一类长度大于 200 个核苷酸、具有有限蛋白编码能力的转录本。核斑周体转录物 1（NEAT1）是一种新鉴定的核限制 lncRNA，它定位于亚核结构，称为斑周体，并以多种方式参与免疫反应。然而，NEAT1 在 IBD 中的作用仍有待充分阐明。在本研究中，通过逆转录-定量聚合酶链反应（RT-qPCR）检测 IBD 血清样本和组织中 NEAT1 lncRNA 的表达水平。此外，通过测定跨上皮电阻以及进行 Western blot 和免疫荧光检测，研究了 NEAT1 对结肠细胞通透性的影响。此外，还进行了葡聚糖硫酸钠实验，以研究下调 NEAT1 对 IBD 小鼠的影响。本研究检测了 NEAT1 在 IBD 细胞和动物模型中的表达水平，以研究抑制 NEAT1 表达后肠道上皮细胞通透性的变化。此外，还研究了不同处理方法对上皮细胞和巨噬细胞表型转化的影响。结果表明，NEAT1 在 IBD 中表达上调，通过调节肠道上皮屏障和通过外泌体介导的巨噬细胞极化参与炎症反应。下调 NEAT1 通过调节肠道上皮屏障和通过外泌体介导的巨噬细胞极化抑制 IBD 中的炎症反应。本研究结果揭示了针对 NEAT1 治疗 IBD 的潜在策略。
