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分析肠道病毒 71 感染致小鼠脑损伤相关 microRNAs。

Analysis of miRNAs Involved in Mouse Brain Damage upon Enterovirus 71 Infection.

机构信息

Center for Infectious Disease Control, Institute of Disease Control and Prevention, Academy of Military Medical SciencesBeijing, China.

The Key Laboratory of Pharmacology and Molecular Biology, Medical College, Henan University of Science and TechnologyLuoyang, China.

出版信息

Front Cell Infect Microbiol. 2017 Apr 19;7:133. doi: 10.3389/fcimb.2017.00133. eCollection 2017.

Abstract

Enterovirus 71 (EV71) infects the central nervous system (CNS) and causes brainstem encephalitis in children. MiRNAs have been found to play various functions in EV71 infection in human cell lines. To identify potential miRNAs involved in the inflammatory injury in CNS, our study, for the first time, performed a miRNA microarray assay using EV71 infected mice brains. Twenty differentially expressed miRNAs were identified (four up- and 16 down-regulated) and confirmed by qRT-PCR. The target genes of these miRNAs were analyzed using KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis, revealing that the miRNAs were mainly involved in the regulation of inflammation and neural system function. MiR-150-5p, -3082-5p, -3473a, -468-3p, -669n, -721, -709, and -5107-5p that regulate MAPK and chemokine signaling were all down-regulated, which might result in increased cytokine production. In addition, miR-3473a could also regulate focal adhesion and leukocyte trans-endothelial migration, suggesting a role in virus-induced blood-brain barrier disruption. The miRNAs and pathways identified in this study could help to understand the intricate interactions between EV71 and the brain injury, offering new insight for the future research of the molecular mechanism of EV71 induced brainstem encephalitis.

摘要

肠道病毒 71 型(EV71)感染中枢神经系统(CNS),并导致儿童脑干脑炎。已经发现 microRNAs 在人类细胞系中的 EV71 感染中发挥各种功能。为了鉴定潜在参与 CNS 炎症损伤的 microRNAs,我们首次使用 EV71 感染的小鼠大脑进行了 microRNA 微阵列分析。鉴定出 20 个差异表达的 microRNAs(4 个上调和 16 个下调),并通过 qRT-PCR 进行了验证。使用 KEGG(京都基因与基因组百科全书)分析对这些 microRNAs 的靶基因进行了分析,表明这些 microRNAs主要参与炎症和神经系统功能的调节。调节 MAPK 和趋化因子信号的 microRNAs-150-5p、-3082-5p、-3473a、-468-3p、-669n、-721、-709 和 -5107-5p 均下调,可能导致细胞因子产生增加。此外,miR-3473a 还可以调节黏附和白细胞跨内皮迁移,提示其在病毒诱导的血脑屏障破坏中起作用。本研究中鉴定的 microRNAs 和途径有助于了解 EV71 与脑损伤之间的复杂相互作用,为 EV71 诱导的脑干脑炎的分子机制的未来研究提供新的见解。

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