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长链非编码 RNA 谱在 LPS 诱导的肠道炎症模型中的研究:对发病机制的新认识。

Long non-coding RNA profiling in LPS-induced intestinal inflammation model: New insight into pathogenesis.

机构信息

Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, PR China.

Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, PR China.

出版信息

Innate Immun. 2019 Nov;25(8):491-502. doi: 10.1177/1753425919872812. Epub 2019 Aug 31.

Abstract

LPS can induce an inflammatory immune response in the intestine, and long non-coding RNA (lncRNA) is involved in the process of inflammatory disease. However, the biological role of lncRNA in the intestinal inflammation of piglets remains unclear. In this study, the lncRNA expression profile of the ileal mucosa of piglets challenged by LPS was analysed using lncRNA sequencing. In total, 112 novel lncRNAs were predicted, of which 58 were up-regulated and 54 down-regulated following LPS challenge. Expression of 15 selected lncRNAs was validated by quantitative PCR. We further investigated the target genes of lncRNA that were enriched in the signalling pathways involved in the inflammatory immune response by utilising Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes analysis, with cell adhesion molecules and mTOR signalling pathway identified. In addition, the co-expression networks between the differentially expressed lncRNAs and the target mRNAs were constructed, with seven core lncRNAs identified, which also demonstrated that the relationship between lncRNAs and the target genes was highly correlated. Our study offers important information about the lncRNAs of the mucosal immune system in piglets and provides new insights into the inflammatory mechanism of LPS challenge, which might serve as a novel target to control intestinal inflammation.

摘要

脂多糖(LPS)可诱发肠道炎症免疫反应,长链非编码 RNA(lncRNA)参与炎症性疾病的发生过程。然而,lncRNA 在仔猪肠道炎症中的生物学作用尚不清楚。本研究采用 lncRNA 测序技术分析 LPS 刺激仔猪回肠黏膜的 lncRNA 表达谱。共预测到 112 个新的 lncRNA,其中 LPS 刺激后 58 个上调,54 个下调。通过定量 PCR 验证了 15 个选定 lncRNA 的表达。通过基因本体论和京都基因与基因组百科全书分析,进一步研究了富集在炎症免疫反应信号通路中的 lncRNA 的靶基因,发现细胞黏附分子和 mTOR 信号通路。此外,构建了差异表达 lncRNA 与靶 mRNAs 之间的共表达网络,鉴定出 7 个核心 lncRNA,这也表明 lncRNA 与靶基因之间的关系高度相关。本研究为仔猪黏膜免疫系统的 lncRNA 提供了重要信息,并为 LPS 刺激的炎症机制提供了新的见解,可能成为控制肠道炎症的新靶点。

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