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Comprehensive analysis of miRNA profiles reveals the role of Schistosoma japonicum miRNAs at different developmental stages.

ABSTRACT: Schistosomiasis is an important zoonotic disease affecting up to 40 kinds of animals and 250 million people. It has been reported that the miRNAs play a role in the metabolism, differentiation, development and reproduction in many organisms. However, the roles of miRNAs regulating the development, maturation and production in schistosome in both females and males remains unclear. Here we present the dynamic transcriptome analysis of all 79 known Schistosoma japonicum miRNAs from pairing to production, including 14 days post-infection (dpi), 16, 18, 20, 22, 24, 26, 28 dpi female and male, by small RNA sequencing. The miRNA expression profiles showed time-related characteristics in male and female from paring to production, which could be clustered into three patterns, characterized by pairing stage highly expressed (cluster 1), maturating stage highly expressed (cluster 2), and egg producing stage highly expressed (cluster 3). The enrichment of miRNA cluster targeted genes in female and male were distinctly different. Network analysis of miRNAs and their target regulation showed that cluster 1 had 15 miRNAs involved in the regulation of interaction, communication, immune response in female-male and parasite-host. The other 11 miRNAs were involved in gender differentiation and the meiotic cell cycle process. In cluster 2, 11 miRNAs were involved in development and sexual maturation. In cluster 3, 45 miRNAs possibly regulate metabolism and synthesis of the substance for egg production. Analysis of the miRNA regulation network would contribute to understanding the molecular mechanism in S. japonicum development and egg production.

SUBMITTER: Yu J

PROVIDER: S-EPMC6449929 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Comprehensive analysis of miRNA profiles reveals the role of Schistosoma japonicum miRNAs at different developmental stages.

Yu Jie J Yu Ying Y Li Qing Q Chen Muxin M Shen Haimo H Zhang RuiXiang R Song Mingxin M Hu Wei W

Veterinary research 20190404 1

Schistosomiasis is an important zoonotic disease affecting up to 40 kinds of animals and 250 million people. It has been reported that the miRNAs play a role in the metabolism, differentiation, development and reproduction in many organisms. However, the roles of miRNAs regulating the development, maturation and production in schistosome in both females and males remains unclear. Here we present the dynamic transcriptome analysis of all 79 known Schistosoma japonicum miRNAs from pairing to produ ...[more]

PMID: 30947738

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Project description:Schistosomes undergo complicated migration in final hosts during infection, associated with differential immune responses. It has been shown that CD4+ T cells play critical roles in response to Schistosoma infections and accumulated documents have indicated that miRNAs tightly regulate T cell activity. However, miRNA profiles in host T cells associated with Schistosoma infection remain poorly characterized. Therefore, we undertook the study and systematically characterized T cell miRNA profiles from the livers and blood of S. japonicum infected C57BL/6J mice at 14- and 21-days post-infection. We observed 508 and 504 miRNAs, in which 264 miRNAs were co-detected in T cells isolated from blood and livers, respectively. The comparative analysis of T cell miRNAs from uninfected and infected C57BL/6J mice blood showed that miR-486b-5p/3p expression was significantly downregulated and linked to various T cell immune responses and miR-375-5p was highly upregulated, associated with Wnt signaling and pluripotency, Delta notch signaling pathways, etc. Whereas hepatic T cells showed miR-466b-3p, miR-486b-3p, miR-1969, and miR-375 were differentially expressed compared to the uninfected control. The different expressions of some miRNAs were further corroborated in isolated T cells from mice and in vitro cultured EL-4 cells treated with S. japonicum worm antigens by RT-qPCR and similar results were found. In addition, bioinformatics analysis combined with RT-qPCR validation of selected targets associated with the immune system and parasite-caused infectious disease showed a significant increase in the expression of Ctla4, Atg5, Hgf, Vcl and Arpc4 and a decreased expression of Fermt3, Pik3r1, Myd88, Nfkbie, Ppp1r12a, Ppp3r1, Nfyb, Atg12, Ube2n, Tyrobp, Cxcr4 and Tollip. Overall, these results unveil the comprehensive repertoire of T cell miRNAs during S. japonicum infection, suggesting that the circulatory (blood) and liver systems have distinct miRNAs landscapes that may be important for regulating T cell immune response. Altogether, our findings indicated a dynamic expression pattern of T cell miRNAs during the hepatic stages of S. japonicum infection.

Project description:Glycans present on glycoproteins and glycolipids of the major human parasite Schistosoma mansoni induce innate as well as adaptive immune responses in the host. To be able to study the molecular characteristics of schistosome infections it is therefore required to determine the expression profiles of glycans and antigenic glycan-motifs during a range of critical stages of the complex schistosome lifecycle. We performed a longitudinal profiling study covering schistosome glycosylation throughout worm- and egg-development using a mass spectrometry-based glycomics approach. Our study revealed that during worm development N-glycans with Galβ1-4(Fucα1-3)GlcNAc (LeX) and core-xylose motifs were rapidly lost after cercariae to schistosomula transformation, whereas GalNAcβ1-4GlcNAc (LDN)-motifs gradually became abundant and predominated in adult worms. LeX-motifs were present on glycolipids up to 2 weeks of schistosomula development, whereas glycolipids with mono- and multifucosylated LDN-motifs remained present up to the adult worm stage. In contrast, expression of complex O-glycans diminished to undetectable levels within days after transformation. During egg development, a rich diversity of N-glycans with fucosylated motifs was expressed, but with α3-core fucose and a high degree of multifucosylated antennae only in mature eggs and miracidia. N-glycan antennae were exclusively LDN-based in miracidia. O-glycans in the mature eggs were also diverse and contained LeX- and multifucosylated LDN, but none of these were associated with miracidia in which we detected only the Galβ1-3(Galβ1-6)GalNAc core glycan. Immature eggs also exhibited short O-glycan core structures only, suggesting that complex fucosylated O-glycans of schistosome eggs are derived primarily from glycoproteins produced by the subshell envelope in the developed egg. Lipid glycans with multifucosylated GlcNAc repeats were present throughout egg development, but with the longer highly fucosylated stretches enriched in mature eggs and miracidia. This global analysis of the developing schistosome's glycome provides new insights into how stage-specifically expressed glycans may contribute to different aspects of schistosome-host interactions.

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Comprehensive analysis of miRNA profiles reveals the role of Schistosoma japonicum miRNAs at different developmental stages.

Publications

Comprehensive analysis of miRNA profiles reveals the role of Schistosoma japonicum miRNAs at different developmental stages.

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