The Precision Medicine Institute, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.
Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China.
J Cell Mol Med. 2021 Jan;25(2):1060-1073. doi: 10.1111/jcmm.16174. Epub 2020 Dec 9.
Intestinal epithelial barrier damage caused by intestinal epithelial cells (IECs) dysfunction plays a crucial role in the pathogenesis and development of inflammatory bowel disease (IBD). Recently, some studies have suggested the emerging role of long non-coding RNAs (lncRNAs) in IBD. The aim of this study was to reveal lncRNAs and mRNA expression profiles in IECs from a mouse model of colitis and to expand our understanding in the intestinal epithelial barrier regulation. IECs from the colons of wild-type mice and dextran sulphate sodium (DSS)-induced mice were isolated for high-throughput RNA-sequencing. A total of 254 up-regulated and 1013 down-regulated mRNAs and 542 up-regulated and 766 down-regulated lncRNAs were detected in the DSS group compared with the Control group. Four mRNAs and six lncRNAs were validated by real-time quantitative PCR. Function analysis showed that dysregulated mRNAs participated in TLR7 signalling pathway, IL-1 receptor activity, BMP receptor binding and IL-17 signalling pathway. Furthermore, the possibility of indirect interactions between differentially expressed mRNAs and lncRNAs was illustrated by the competing endogenous RNA (ceRNA) network. LncRNA ENSMUST00000128026 was predicted to bind to mmu-miR-6899-3p, regulating Dnmbp expression. LncRNA NONMMUT143162.1 was predicted to competitively bind to mmu-miR-6899-3p, regulating Tnip3 expression. Finally, the protein-protein interaction (PPI) network analysis was constructed with 311 nodes and 563 edges. And the highest connectivity degrees were Mmp9, Fpr2 and Ccl3. These results provide novel insights into the functions of lncRNAs and mRNAs involved in the regulation of the intestinal epithelial barrier.
肠上皮细胞(IECs)功能障碍导致的肠上皮屏障损伤在炎症性肠病(IBD)的发病机制和发展中起关键作用。最近,一些研究表明长链非编码 RNA(lncRNAs)在 IBD 中具有新的作用。本研究旨在揭示结肠炎小鼠模型中 IECs 的 lncRNA 和 mRNA 表达谱,并扩展我们对肠道上皮屏障调节的理解。从野生型小鼠和葡聚糖硫酸钠(DSS)诱导的小鼠的结肠中分离 IECs 进行高通量 RNA 测序。与对照组相比,DSS 组中共有 254 个上调和 1013 个下调的 mRNAs 以及 542 个上调和 766 个下调的 lncRNAs。通过实时定量 PCR 验证了 4 个 mRNAs 和 6 个 lncRNAs。功能分析表明,失调的 mRNAs 参与 TLR7 信号通路、IL-1 受体活性、BMP 受体结合和 IL-17 信号通路。此外,通过竞争内源性 RNA(ceRNA)网络说明了差异表达的 mRNAs 和 lncRNAs 之间可能存在间接相互作用。预测 lncRNA ENSMUST00000128026 与 mmu-miR-6899-3p 结合,调节 Dnmbp 的表达。预测 lncRNA NONMMUT143162.1 与 mmu-miR-6899-3p 竞争结合,调节 Tnip3 的表达。最后,构建了具有 311 个节点和 563 个边的蛋白质-蛋白质相互作用(PPI)网络。并且具有最高连接度的是 Mmp9、Fpr2 和 Ccl3。这些结果为 lncRNAs 和 mRNAs 参与肠道上皮屏障调节的功能提供了新的见解。