Department of Liver Surgery and Liver Transplantation Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Institute of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
J Dig Dis. 2019 Jun;20(6):308-317. doi: 10.1111/1751-2980.12749. Epub 2019 May 20.
To explore the expression profile and role of hepatic long non-coding RNA (lncRNA) in acetaminophen-induced liver injury mouse model by analyzing lncRNA-mRNA co-expression.
Serum aminotransferase, liver pathology and inflammatory cells were analyzed in mice model at different time points after treated with acetaminophen 300 mg/kg. High-throughput RNA sequencing was performed to investigate hepatic expression profiles of messenger RNA (mRNA) and lncRNA. The relationship between the lncRNA and mRNA was delineated by the co-expression network using Cytoscape software. Differential mRNAs co-expressed with lncRNAs were analyzed using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment. Differential mRNAs and lncRNAs were selected for quantitative reverse transcription polymerase chain reaction validation, and the conservation of lncRNA between human and mouse was analyzed.
Liver injury was more severe at 24 hours than at 6 hours. There was a substantial infiltration of monocytes instead of neutrophil and Kupffer cells at 24 hours compared with 6 hours. The mRNAs co-expressed with the differential lncRNAs at 24 vs 6 hours were mainly enriched in protein processing in endoplasmic reticulum, MAPK and PPAR signaling pathways. The co-expression network delineated with four lncRNAs and 94 mRNAs presented the core position of lncRNA in the network. A conservation analysis indicated that four differential mouse lncRNAs (NONMMUT023651.2, NONMMUT029382.2, NONMMUT029383.2 and NONMMUT102053.1) could all be mapped to the relevant human lncRNAs.
Four lncRNAs may play regulatory roles through metabolic and apoptosis-related pathways during hepatic homeostasis maintenance and repair progress.
通过分析长链非编码 RNA（lncRNA）-mRNA 共表达，探讨肝损伤小鼠模型中肝组织长链非编码 RNA 的表达谱和作用。
用 300mg/kg 对乙酰氨基酚处理小鼠后，在不同时间点检测血清转氨酶、肝脏病理和炎症细胞。采用高通量 RNA 测序技术研究信使 RNA（mRNA）和 lncRNA 的肝组织表达谱。使用 Cytoscape 软件的共表达网络描绘 lncRNA 与 mRNA 之间的关系。采用基因本体论和京都基因与基因组百科全书富集分析差异表达的 lncRNA 与 mRNA。采用定量逆转录聚合酶链反应验证差异表达的 mRNA 和 lncRNA，并分析 lncRNA 在人和小鼠之间的保守性。
与 6 小时相比，24 小时肝损伤更严重。与 6 小时相比，24 小时单核细胞浸润明显增多，而中性粒细胞和枯否细胞浸润减少。与 24 小时相比，6 小时差异表达的 lncRNA 共表达的 mRNAs 主要富集在蛋白质加工内质网、MAPK 和 PPAR 信号通路。用 4 个 lncRNA 和 94 个 mRNAs 描绘的共表达网络显示了 lncRNA 在网络中的核心位置。保守性分析表明，4 个差异表达的小鼠 lncRNA（NONMMUT023651.2、NONMMUT029382.2、NONMMUT029383.2 和 NONMMUT102053.1）均可映射到相应的人类 lncRNA。
在肝内稳态维持和修复过程中，4 个 lncRNA 可能通过代谢和凋亡相关途径发挥调节作用。
