Dysregulation of hepatic microRNA expression in C57BL/6 mice affected by excretory-secretory products of Fasciola gigantica

文献类型： 外文期刊

第一作者： Shi, Wei

作者： Shi, Wei;He, Jun-Jun;Zhu, Xing-Quan;Shi, Wei;Mei, Xue-Fang;Lu, Ke-Jing;Zeng, Zi-Xuan;Zhang, Yao-Yao;Sheng, Zhao-An;Huang, Wei-Yi;Shi, Wei;Elsheikha, Hany M.;Zhu, Xing-Quan

作者机构：

期刊名称：PLOS NEGLECTED TROPICAL DISEASES （ 影响因子：4.411； 五年影响因子：4.898 ）

ISSN： 1935-2735

年卷期： 2020 年 14 卷 12 期

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收录情况： SCI

摘要： Author summary Fasciolosis is a worldwide neglected parasitic disease which is caused by the infections of liver flukes, such as Fasciola hepatica and Fasciola gigantica. The excretory-secretory products released by F. gigantica (FgESPs) play important roles in regulating host biological processes. However, the regulation mechanism remains unclear. This study used high-throughput RNA sequencing to describe the comprehensive small RNA profile altered by FgESPs stimulation. We manifested that weeks of FgESPs exposure lead to a possible hypo-reactiveness and the small RNA profile was significantly altered, especially at 4 weeks post exposure. GO and KEGG pathway analyses of DEmiRNAs targets showed that FgESPs participate in regulation of neural activities, digestive function, and immune responses of host, alter several host cellular components or functions such as cell membrane, cellular communication, organelle and checking of DNA damage. The findings of this study reveal the small RNA profile changes following FgESPs stimulation, providing novel data for elucidating the interaction between Fasciola gigantica and infected host. The excretory-secretory products released by the liver fluke Fasciola gigantica (FgESPs) play important roles in regulating the host immune response during the infection. Identification of hepatic miRNAs altered by FgESPs may improve our understanding of the pathogenesis of F. gigantica infection. In this study, we investigated the alterations in the hepatic microRNAs (miRNAs) in mice treated with FgESPs using high-throughput small RNA (sRNA) sequencing and bioinformatics analysis. The expression of seven miRNAs was confirmed by quantitative stem-loop reverse transcription quantitative PCR (qRT-PCR). A total of 1,313 miRNAs were identified in the liver of mice, and the differentially expressed (DE) miRNAs varied across the time lapsed post exposure to FgESPs. We identified 67, 154 and 53 dysregulated miRNAs at 1, 4 and 12 weeks post-exposure, respectively. 5 miRNAs (miR-126a-3p, miR-150-5p, miR-155-5p, miR-181a-5p and miR-362-3p) were commonly dysregulated at the three time points. We also found that most of the DE miRNAs were induced by FgESPs in the mouse liver after 4 weeks of exposure. These were subjected to Gene Ontology (GO) enrichment analysis, which showed that the predicted targets of the hepatic DE miRNAs of mice 4 weeks of FgESPs injection were enriched in GO terms, including cell membrane, ion binding, cellular communication, organelle and DNA damage. KEGG analysis indicated that the predicted targets of the most downregulated miRNAs were involved in 15 neural activity-related pathways, 6 digestion-related pathways, 20 immune response-related pathways and 17 cancer-related pathways. These data provide new insights into how FgESPs can dysregulate hepatic miRNAs, which play important roles in modulating several aspects of F. gigantica pathogenesis.

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