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卵源性细胞外囊泡中的Sja-miR-71a通过靶向信号素4D抑制血吸虫病引起的肝纤维化。

Sja-miR-71a in egg-derived extracellular vesicles suppresses liver fibrosis caused by schistosomiasis via targeting semaphorin 4D.

作者信息

Wang Lifu, Liao Yao, Yang Ruibing, Yu Zilong, Zhang Lichao, Zhu Zifeng, Wu Xiaoying, Shen Jia, Liu Jiahua, Xu Lian, Wu Zhongdao, Sun Xi

机构信息

Department of Parasitology of Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.

Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, China.

出版信息

J Extracell Vesicles. 2020 Jul 9;9(1):1785738. doi: 10.1080/20013078.2020.1785738.

DOI:10.1080/20013078.2020.1785738
PMID:32944173
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7480424/
Abstract

Schistosomiasis is characterized by liver fibrosis, and studies have indicated that () eggs can limit the progression of liver fibrosis. However, the detailed molecular mechanisms are yet unclear. Extracellular vesicles (EVs) contain a selection of miRNAs for long-distance exchange of information and act as an important pathway for host-parasite communication. This study aimed to explore the potential role of egg-derived EVs and its key miRNA in liver fibrosis. Herein, we found that egg-derived EVs can inhibit the activation of hepatic stellate cells, which is mediated via the high expression of Sja-miR-71a. Sja-miR-71a in EVs attenuates the pathological progression and liver fibrosis in infection. Sja-miR-71a inhibiting TGF-β1/SMAD and interleukin (IL)-13/STAT6 pathways via directly targeting semaphorin 4D (Sema4D). In addition, Sja-miR-71a can also suppress liver fibrosis by regulating Th1/Th2/Th17 and Treg balance. This study contributes to further understanding of the molecular mechanisms underlying -host interactions, and Sema4D may be a potential target for schistosomiasis liver fibrosis treatment.

摘要

血吸虫病的特征是肝纤维化,研究表明()虫卵可以限制肝纤维化的进展。然而,具体的分子机制尚不清楚。细胞外囊泡(EVs)包含多种用于远距离信息交换的微小RNA(miRNAs),并作为宿主-寄生虫通信的重要途径。本研究旨在探讨虫卵来源的细胞外囊泡及其关键微小RNA在肝纤维化中的潜在作用。在此,我们发现虫卵来源的细胞外囊泡可以抑制肝星状细胞的激活,这是通过Sja-miR-71a的高表达介导的。细胞外囊泡中的Sja-miR-71a减轻了()感染中的病理进展和肝纤维化。Sja-miR-71a通过直接靶向信号素4D(Sema4D)抑制转化生长因子-β1(TGF-β1)/SMAD和白细胞介素(IL)-13/信号转导和转录激活因子6(STAT6)通路。此外,Sja-miR-71a还可以通过调节Th1/Th2/Th17和调节性T细胞(Treg)平衡来抑制肝纤维化。本研究有助于进一步了解()与宿主相互作用的分子机制,并且信号素4D可能是血吸虫病肝纤维化治疗的潜在靶点。

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