Abstract
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.
Highlights
Fasciolosis is a worldwide parasitic disease caused by the liver flukes Fasciola hepatica and Fasciola gigantica [1]
An average of 55.0% of the unique sequences were defined as miRNAs, less than 0.01% were novel miRNAs, 35% were unannotated, and the rests were other known categories of identified small RNA, including rRNA, tRNA, snRNA, snoRNA, gene intron/exon, etc (Fig 1)
The present study identified the dynamic global miRNA expression pattern in mice livers triggered by short- or long-term exposure to FgESPs, based on high-throughput sequencing approach
Summary
Fasciolosis is a worldwide parasitic disease caused by the liver flukes Fasciola hepatica and Fasciola gigantica [1]. The pathogenic effects of these liver flukes are caused by direct physical interaction with the host tissue and through exposure to their excretory-secretory products (ESPs). Proteomic analysis of ESPs released by F. gigantica (hereinafter referred to as “FgESPs”) has identified over one hundred proteins, and the composition of FgESPs varies with the development of the flukes. The annotated proteins belong to cathepsin family, glutathione S-transferases, calcium-binding proteins, and some catalytic activity and cellular process-relevant proteins, and many of them correlate with the regulation of host immune response; while the functions of most of other protein components are unknown [8]. Given the complexity and uncertainty of components and biological/immunological functions involved in ESPs, more researches are still required to elucidate the precise mechanisms by which FgESPs modulate the host immune response
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