Department of Health and Disease Management, School of Nursing, Binzhou Medical University, Guanhai Road 346, Yantai, Shandong, 264000, China.
Department of Anesthesia, Binzhou Medical University Hospital, Binzhou, Shandong, 256600, China.
Acta Trop. 2023 Nov;247:107012. doi: 10.1016/j.actatropica.2023.107012. Epub 2023 Aug 31.
Schistosomiasis is a prevalent infectious disease caused by the parasitic trematodes of the genus Schistosoma. Praziquantel (PZQ), a safe and affordable drug, is the recommended oral treatment for schistosomiasis. The main pathologic manifestation of schistosomiasis is liver injury. However, the role and interactions of various RNA molecules in the effect of PZQ on the liver after S. japonicum infection have not been elucidated.
In this study, C57BL/6 mice were randomly divided into the control group, infection group, and PZQ treatment group. Total RNA was extracted from the livers of the mice. High-throughput whole transcriptome sequencing was performed to detect the RNA expression profiles in the three groups. A co-expression gene-interaction network was established based on the significant differentially expressed genes in the PZQ treatment group; messenger RNA (mRNA) Cyp4a14 was identified as a critical hub gene. Furthermore, competitive endogenous RNA networks were constructed by predicting the specific binding relations between mRNA and long noncoding (lnc) RNA and between lncRNA and microRNA (miRNA) of Cyp4a14, suggesting the involvement of the H19/miR-130b-3p/Cyp4a14 regulatory axis. Dual luciferase reporter assay result proved the specific binding of miR-130b-3p with Cyp4a14 3'UTR.
Our findings indicate the involvement of the H19/miR-130b-3p/Cyp4a14 axis in the effect of PZQ on the liver after S. japonicum infection. Moreover, the expression of mRNA Cyp4a14 could be regulated by the bonding of miR-130b-3p with 3'UTR of Cyp4a14. The findings of this study could provide a novel perspective to understand the host response to PZQ against S. japonicum in the future.
血吸虫病是一种由血吸虫属寄生虫引起的流行传染病。吡喹酮（PZQ）是一种安全且负担得起的药物，是治疗血吸虫病的推荐口服药物。血吸虫病的主要病理表现为肝损伤。然而，在日本血吸虫感染后，PZQ 对肝脏的作用以及各种 RNA 分子的作用和相互作用尚不清楚。
本研究将 C57BL/6 小鼠随机分为对照组、感染组和 PZQ 治疗组。从各组小鼠的肝脏中提取总 RNA。采用高通量全转录组测序检测三组小鼠的 RNA 表达谱。根据 PZQ 治疗组中显著差异表达基因建立共表达基因-互作网络，鉴定出信使 RNA（mRNA）Cyp4a14 为关键枢纽基因。此外，通过预测 Cyp4a14 的 mRNA 和长链非编码（lnc）RNA 以及 lncRNA 和 microRNA（miRNA）之间的特定结合关系构建竞争性内源性 RNA 网络，提示 H19/miR-130b-3p/Cyp4a14 调控轴的参与。双荧光素酶报告基因检测结果证实了 miR-130b-3p 与 Cyp4a14 3'UTR 的特异性结合。
我们的研究结果表明，H19/miR-130b-3p/Cyp4a14 轴参与了日本血吸虫感染后 PZQ 对肝脏的作用。此外，miR-130b-3p 与 Cyp4a14 3'UTR 的结合可以调节 Cyp4a14 mRNA 的表达。本研究的发现为今后理解宿主对 PZQ 抗日本血吸虫的反应提供了新的视角。
