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泡状原头蚴经肝门静脉感染条件下miRNAs对肝损伤的机制研究

Study on the mechanism of miRNAs on liver injury in the condition of Protoscocephalus alveolarus transhepatic portal vein infection.

作者信息

Zhu Yazhou, Li Ming, Li Zihua, Song Jiahui, Zhao Wei

机构信息

Department of Pathogen Biology, School of Basic Medicine, Ningxia Medical University, Yinchuan, China.

Ningxia Key Laboratory of Prevention and Control of Common Infectious Diseases, Yinchuan, China.

出版信息

Immun Inflamm Dis. 2024 Apr;12(4):e1236. doi: 10.1002/iid3.1236.

Abstract

OBJECTIVE

To explore the role of miRNA in liver damage caused by Echinococcus multilocularis infection.

METHODS

Six female C57BL mice were randomly divided into two groups, the control group and the infection group. Mice in the control group were injected with 100 μL PBS through the hepatic portal vein, and mice in the infection group were infected with E. multilocularis via the hepatic portal vein to establish a mouse model of infection. Small RNA sequencing was performed for detecting the expression of miRNAs in the liver of mice infected with 2000 E. multilocularis after 3 months of infection, screen out miRNAs related to liver damage, and verify by RT-PCR.

RESULTS

Seventy-one differentially expressed miRNAs were found in the liver in comparison with control, and a total of 36 mouse miRNAs with |FC| >0.585 were screened out, respectively. In addition, Targetscan (V5.0) and miRanda (v3.3a) software were used to predict differential miRNAs target genes and functional enrichment of target genes. Functional annotation showed that "cytokine-cytokine interaction," "positive regulation of cytokine production," "inflammatory response," and "leukocyte activation" were enriched in the liver of E. multilocularis-infected mice. Moreover, the pathways "human cytomegalovirus infection," "cysteine and methionine metabolism," "Notch signaling pathway," and "ferroptosis" were involved in liver disease. Furthermore, four miRNAs (mmu-miR-30e-3p, mmu-miR-203-3p, mmu-miR-125b-5p, and mmu-miR-30c-2-3p) related to liver injury were screened and verified.

CONCLUSION

This study revealed that the expression profiling of miRNAs in the livers was changed after E. multilocularis infection, and improved our understanding of the transcriptomic landscape of hepatic echinococcosis in mice.

摘要

目的

探讨微小RNA(miRNA)在多房棘球绦虫感染所致肝损伤中的作用。

方法

将6只雌性C57BL小鼠随机分为两组,即对照组和感染组。对照组小鼠经肝门静脉注射100 μL磷酸盐缓冲液(PBS),感染组小鼠经肝门静脉感染多房棘球绦虫以建立感染小鼠模型。感染3个月后,对感染2000条多房棘球绦虫的小鼠肝脏进行小RNA测序,以检测miRNA的表达,筛选出与肝损伤相关的miRNA,并通过逆转录聚合酶链反应(RT-PCR)进行验证。

结果

与对照组相比,在肝脏中发现71个差异表达的miRNA,分别筛选出共36个|倍数变化(FC)|>0.585的小鼠miRNA。此外,使用Targetscan(V5.0)和miRanda(v3.3a)软件预测差异miRNA的靶基因以及靶基因的功能富集情况。功能注释显示,“细胞因子-细胞因子相互作用”“细胞因子产生的正调控”“炎症反应”和“白细胞活化”在多房棘球绦虫感染小鼠的肝脏中富集。此外,“人巨细胞病毒感染”“半胱氨酸和甲硫氨酸代谢”“Notch信号通路”和“铁死亡”等通路与肝脏疾病有关。此外,筛选并验证了4个与肝损伤相关的miRNA(小鼠miR-30e-3p、小鼠miR-203-3p、小鼠miR-125b-5p和小鼠miR-30c-2-3p)。

结论

本研究揭示了多房棘球绦虫感染后小鼠肝脏中miRNA的表达谱发生了变化,并增进了我们对小鼠肝包虫病转录组景观的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5df9/11037255/800312049906/IID3-12-e1236-g006.jpg

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