Zhang Nan-Nan, Zhang Yi, Wang Lu, Xia Jin-Gen, Liang Shun-Tao, Wang Yan, Wang Zhi-Zhi, Huang Xu, Li Min, Zeng Hui, Zhan Qing-Yuan
Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China.
Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China.
J Cell Biochem. 2019 Jul;120(7):11660-11679. doi: 10.1002/jcb.28446. Epub 2019 Feb 19.
The key regulators of inflammation underlying ventilator-induced lung injury (VILI) remain poorly defined. Long noncoding RNAs (lncRNAs) have been implicated in the inflammatory response of many diseases; however, their roles in VILI remain unclear. We, therefore, performed transcriptome profiling of lncRNA and messenger RNA (mRNA) using RNA sequencing in lungs collected from mice model of VILI and control groups. Gene expression was analyzed through RNA sequencing and quantitative reverse transctiption polymerase chain reaction. A comprehensive bioinformatics analysis was used to characterize the expression profiles and relevant biological functions and for multiple comparisons among the controls and the injury models at different time points. Finally, lncRNA-mRNA coexpression networks were constructed and dysregulated lncRNAs were analyzed functionally. The mRNA transcript profiling, coexpression network analysis, and functional analysis of altered lncRNAs indicated enrichment in the regulation of immune system/inflammation processes, response to stress, and inflammatory pathways. We identified the lncRNA Gm43181 might be related to lung damage and neutrophil activation via chemokine receptor chemokine (C-X-C) receptor 2. In summary, our study provides an identification of aberrant lncRNA alterations involved in inflammation upon VILI, and lncRNA-mediated regulatory patterns may contribute to VILI inflammation.
机械通气诱导性肺损伤(VILI)潜在的关键炎症调节因子仍未明确。长链非编码RNA(lncRNA)与多种疾病的炎症反应有关;然而,它们在VILI中的作用仍不清楚。因此,我们使用RNA测序对VILI小鼠模型和对照组收集的肺组织进行了lncRNA和信使RNA(mRNA)的转录组分析。通过RNA测序和定量逆转录聚合酶链反应分析基因表达。采用全面的生物信息学分析来表征表达谱和相关生物学功能,并在不同时间点的对照组和损伤模型之间进行多重比较。最后,构建lncRNA-mRNA共表达网络,并对失调的lncRNA进行功能分析。mRNA转录谱分析、共表达网络分析以及lncRNA改变的功能分析表明,免疫系统/炎症过程的调节、应激反应和炎症途径中存在富集。我们发现lncRNA Gm43181可能通过趋化因子受体趋化因子(C-X-C)受体2与肺损伤和中性粒细胞激活有关。总之,我们的研究确定了VILI炎症中涉及的异常lncRNA改变,并且lncRNA介导的调节模式可能导致VILI炎症。