Luo Honglin, Zhang Yaoyao, Sheng Zhaoan, Luo Tao, Chen Jie, Liu Junjie, Wang Huifeng, Chen Miao, Shi Yunliang, Li Lequn
Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China.
Guangxi Key Laboratory for Aquatic Genetic Breeding and Healthy Aquaculture, Guangxi Institute of Fishery Sciences, Nanning, China.
Cell Physiol Biochem. 2018;47(2):505-522. doi: 10.1159/000489984. Epub 2018 May 22.
BACKGROUND/AIMS: Long noncoding RNAs (lncRNAs) are well known regulators of gene expression that play essential roles in macrophage activation and polarization. However, the role of lncRNA in Fasciola gigantica excretory/secretory products (ESP)-induced M2 polarization into M1 macrophages is unclear. Herein, we performed lncRNA profiling of lncRNAs and mRNAs during the ESP-induced macrophage polarization process.
F. gigantica ESP was used to induce peritoneal cavity M2 macrophages in BALB/c mice (5-6 weeks old) in vivo, and these cells were subsequently isolated and stimulated with IFN-γ + LPS to induce M1 cells in vitro. LncRNA and mRNA profiling was performed via microarray at the end of both polarization stages.
In total, 2,844 lncRNAs (1,579 upregulated and 1,265 downregulated) and 1,782 mRNAs (789 upregulated and 993 downregulated) were differentially expressed in M2 macrophages compared to M1 macrophages, and six lncRNAs were identified during polarization. We selected 34 differentially expressed lncRNAs and mRNAs to validate the results of microarray analysis using quantitative real-time PCR (qPCR). Pathway and Gene Ontology (GO) analyses demonstrated that these altered transcripts were involved in multiple biological processes, particularly peptidase activity and carbohydrate metabolism. Furthermore, coding and non-coding gene (CNC) and mRNA-related ceRNA network analyses were conducted to predict lncRNA expression trends and the potential target genes of these lncRNAs and mRNAs. Moreover, we determined that four lncRNAs and four mRNAs might participate in F. gigantica ESP-induced M2 polarization into M1 macrophages.
This study illustrates the basic profiling of lncRNAs and mRNAs during F. gigantica ESP-induced M2 polarization into M1 macrophages and deepens our understanding of the mechanism underlying this process.
背景/目的：长链非编码RNA（lncRNA）是众所周知的基因表达调节因子，在巨噬细胞活化和极化中发挥重要作用。然而，lncRNA在巨片形吸虫排泄/分泌产物（ESP）诱导M2巨噬细胞向M1巨噬细胞极化中的作用尚不清楚。在此，我们对ESP诱导巨噬细胞极化过程中的lncRNA和mRNA进行了分析。
用巨片形吸虫ESP在体内诱导BALB/c小鼠（5 - 6周龄）腹腔M2巨噬细胞，随后分离这些细胞并用IFN-γ + LPS刺激以在体外诱导M1细胞。在两个极化阶段结束时通过微阵列进行lncRNA和mRNA分析。
与M1巨噬细胞相比，M2巨噬细胞中总共2844个lncRNA（1579个上调和1265个下调）和1782个mRNA（789个上调和993个下调）差异表达，并且在极化过程中鉴定出6个lncRNA。我们选择了34个差异表达的lncRNA和mRNA，使用定量实时PCR（qPCR）验证微阵列分析结果。通路和基因本体（GO）分析表明，这些改变的转录本参与多个生物学过程，特别是肽酶活性和碳水化合物代谢。此外，进行了编码和非编码基因（CNC）以及与mRNA相关的ceRNA网络分析，以预测lncRNA表达趋势以及这些lncRNA和mRNA的潜在靶基因。此外，我们确定4个lncRNA和4个mRNA可能参与巨片形吸虫ESP诱导的M2巨噬细胞向M1巨噬细胞的极化过程。
本研究阐明了巨片形吸虫ESP诱导M2巨噬细胞向M1巨噬细胞极化过程中lncRNA和mRNA的基本图谱，加深了我们对该过程潜在机制的理解。
