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小胶质细胞激活早期阶段的mRNA、lncRNA和circRNA的综合分析

Comprehensive analysis of mRNAs, lncRNAs and circRNAs in the early phase of microglial activation.

作者信息

Wen Jiagen, Liu Yujie, Zhan Zhen, Chen Shiqing, Hu Bingfeng, Ge Jinfang, Xie Qilian

机构信息

Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, Anhui 230051, P.R. China.

Department of Gynecology and Obstetrics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, P.R. China.

出版信息

Exp Ther Med. 2021 Dec;22(6):1460. doi: 10.3892/etm.2021.10895. Epub 2021 Oct 20.

DOI:10.3892/etm.2021.10895
PMID:34737800
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8561759/
Abstract

Sepsis-associated encephalopathy (SAE) is a common complication of sepsis that may seriously affect the prognosis and quality of life of patients with sepsis. Microglial activation is vital to the neuroinflammation and the pathology of SAE. In the present study, cultured BV-2 microglial cells stimulated with lipopolysaccharide (LPS) were employed as a model of microglia activation. The altered profiles of long noncoding (lnc)RNAs, circular (circ)RNAs and mRNAs in BV-2 cells after 4 h of LPS exposure were arrayed by using the Agilent competing endogenous (ce)RNA Microarray Chip. Using fold change >2 and P<0.05 as the cutoff criteria, 1,135 mRNAs and 2,488 lncRNAs were determined to be upregulated and 630 mRNAs and 744 lncRNAs to be downregulated. The number of differentially expressed circRNAs was lower, with 140 upregulated and 123 downregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of DE mRNAs suggested that inflammatory responses, as well as lipid metabolism, were involved in microglial activation. Furthermore, analyses of ceRNA networks of the lncRNA-miRNA-mRNA or circRNA-miRNA-mRNA interrelations were performed. The present study revealed a multitude of novel candidate mRNAs, lncRNAs and circRNAs involved in microglial activation, which may improve the current knowledge on neuroinflammation and provide potential therapeutic targets for SAE.

摘要

脓毒症相关脑病(SAE)是脓毒症的常见并发症,可严重影响脓毒症患者的预后和生活质量。小胶质细胞活化对SAE的神经炎症和病理过程至关重要。在本研究中,用脂多糖(LPS)刺激培养的BV-2小胶质细胞作为小胶质细胞活化模型。使用安捷伦竞争性内源(ce)RNA微阵列芯片对LPS暴露4小时后BV-2细胞中长链非编码(lnc)RNA、环状(circ)RNA和mRNA的变化图谱进行阵列分析。以变化倍数>2且P<0.05作为截断标准,确定1135个mRNA和2488个lncRNA上调,630个mRNA和744个lncRNA下调。差异表达的circRNA数量较少,其中140个上调,123个下调。对差异表达mRNA的基因本体论和京都基因与基因组百科全书分析表明,炎症反应以及脂质代谢参与了小胶质细胞活化。此外,还对lncRNA-miRNA-mRNA或circRNA-miRNA-mRNA相互关系的ceRNA网络进行了分析。本研究揭示了许多参与小胶质细胞活化的新型候选mRNA、lncRNA和circRNA,这可能增进当前对神经炎症的认识,并为SAE提供潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f80/8561759/5fcbea235ae5/etm-22-06-10895-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f80/8561759/340c3d97a85f/etm-22-06-10895-g00.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f80/8561759/340c3d97a85f/etm-22-06-10895-g00.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f80/8561759/3a5c3f5e2929/etm-22-06-10895-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f80/8561759/2766da1ba6d7/etm-22-06-10895-g03.jpg
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