School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
Acta Trop. 2022 Jan;225:106200. doi: 10.1016/j.actatropica.2021.106200. Epub 2021 Nov 2.
Schistosomiasis, caused by a parasite with a wide range of mammalian hosts, remains one of the most prevailing parasitic diseases in the world. While numerous studies have reported that the growth and reproduction of schistosomes in immunodeficient mice was significantly retarded, the underlying molecular mechanisms have yet to be revealed. In this study, we comparatively analyzed the microRNA expression of Schistosoma japonicum derived from SCID and BALB/c mice on the 35 day post-infection by high-throughput RNA sequencing as prominent morphological abnormalities had been observed in schistosomes from SCID mice when compared with those from BALB/c mice. The results revealed that more than 72% and 61% of clean reads in the small RNA libraries of female and male schistosomes, respectively, could be mapped to the selected miRs in the miRBase or the sequences of species-specific genomes. Further analysis identified 122 miRNAs using TPM >0.01 as the threshold value, including 75 known and 47 novel miRNAs, 96 of which were commonly expressed across all the four tested schistosome libraries. Comparative analysis of the libraries of schistosomes from SCID and BALB/c mice identified 15 differentially expressed miRNAs (5 up-regulated and 10 down-regulated) among females and 16 among males (9 up-regulated and 7 down-regulated). Integrated analysis of the two sets of differentially expressed miRNAs of female and male worms identified 2 miRNAs (sja-miR-3488 and sja-miR-novel_29) that overlapped between female and male datasets. Prediction of miRNA targets and Gene Ontology (GO) term enrichment analysis of the predicted target genes revealed that these genes were involved in some important biological processes, such as nucleic acid metabolic process, macromolecule modification, and cellular aromatic compound metabolic process. The predicted target genes were further matched to the differentially expressed genes in male and female schistosomes from the above two hosts, obtaining 7 genes that may be responsible for regulating the growth, development and sex maturation of schistosomes. Taken together, this study provides the first identification of differentially expressed miRNAs in schistosomes from SCID and BALB/c mice. These miRNAs and their predicted target mRNAs are probably involved in the regulation of development, growth, and maturation of schistosomes. Therefore, this study expands our understanding of schistosome development regulation and host-parasite relationship, and also provides a valuable set of potential anti-schistosomal targets for prevention and control of schistosomiasis.
日本血吸虫病是一种由广泛宿主哺乳动物寄生虫引起的疾病，仍然是世界上最流行的寄生虫病之一。虽然许多研究报告称，免疫缺陷小鼠中的血吸虫的生长和繁殖明显受到抑制，但潜在的分子机制尚未被揭示。在这项研究中，我们通过高通量 RNA 测序比较分析了来自 SCID 和 BALB/c 小鼠的日本血吸虫在感染后 35 天的 microRNA 表达，因为与 BALB/c 小鼠相比，SCID 小鼠中的血吸虫表现出明显的形态异常。结果表明，雌性和雄性血吸虫小 RNA 文库的清洁读数中，分别有超过 72%和 61%可以映射到 miRBase 中的选定 miRs 或种特异性基因组的序列。进一步分析使用 TPM > 0.01 作为阈值值鉴定了 122 个 miRNA，包括 75 个已知和 47 个新的 miRNA，其中 96 个在所有四个测试的血吸虫文库中普遍表达。SCID 和 BALB/c 小鼠来源的血吸虫文库之间的比较分析鉴定出 15 个差异表达 miRNA（5 个上调和 10 个下调），其中雌性有 16 个，雄性有 16 个（9 个上调和 7 个下调）。雌性和雄性蠕虫的两组差异表达 miRNA 的综合分析鉴定出 2 个 miRNA（sja-miR-3488 和 sja-miR-novel_29）在雌性和雄性数据集之间重叠。miRNA 靶标的预测和预测靶基因的基因本体论 (GO) 术语富集分析表明，这些基因参与了一些重要的生物过程，如核酸代谢过程、大分子修饰和细胞芳香化合物代谢过程。预测的靶基因进一步与上述两种宿主来源的雄性和雌性血吸虫中的差异表达基因匹配，获得了 7 个可能负责调节血吸虫生长、发育和性成熟的基因。总之，本研究首次鉴定了 SCID 和 BALB/c 小鼠来源的血吸虫中的差异表达 miRNA。这些 miRNA 及其预测的靶 mRNA 可能参与了血吸虫的发育、生长和成熟的调节。因此，本研究扩展了我们对血吸虫发育调控和宿主-寄生虫关系的理解，为血吸虫病的防治提供了一组有价值的潜在抗血吸虫靶点。
