Exosomal miRNAs in the plasma of Cynoglossus semilaevis infected with Vibrio harveyi: Pleiotropic regulators and potential biomarkers involved in inflammatory and immune responses.

Exosomal miRNAs in the plasma of Cynoglossus semilaevis infected with Vibrio harveyi: Pleiotropic regulators and potential biomarkers involved in inflammatory and immune responses.
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DOI:
10.3389/fimmu.2022.949670
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发表时间:
2022
影响因子:
7.3
通讯作者:
--
中科院分区:
医学2区
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外泌体是一类直径在约50至150 nm范围内的细胞外囊泡。外泌体广泛存在于生物体液中,广泛参与多种生理和病理过程中的细胞内信息传递,是一种很有前途的生物标志物,可用于多种疾病的诊断和预后。越来越多的证据表明,外泌体在细菌感染的炎症和免疫反应中也起着重要作用。然而,硬骨鱼类外来体的研究仍然很少。本研究以哈维氏弧菌(Vibrio harveyi)感染半滑舌鳎(Cynoglossus semilaevis)为研究对象,研究了其血浆中外泌体microRNA(miRNAs)的变化。在细菌挑战后,在早期(6和16 h)和晚期阶段对血浆进行采样。(48、72和96 h)感染,随后进行外泌体分离和外泌体miRNA测序。结果显示,85个外泌体miRNAs的表达谱在对照组、早期感染组和晚期感染组之间存在显著差异。基因本体论(GO)和京都基因和基因组百科全书(KEGG)富集分析显示,外泌体miRNA靶向的预测基因广泛参与多种炎症和免疫过程,提示血浆中的一系列过程都受到外泌体miRNA的调控,包括病原体的入侵和识别以及与细胞因子产生相关的信号通路的激活和调节。此外,脾脏被发现是外泌体富集的偏好,并且ZC3H12A、ARID5A和外泌体ssa-miR-146a-5p调节白细胞介素-6产生的潜在机制可能存在于中国滑舌鳎中。此外,ssa-miR-146a-5p和nbr-miR-731在感染组的血浆外泌体和脾脏中的水平升高,表明它们可作为生物标志物用于预测和诊断哈氏弧菌感染。因此,本研究中的集体结果表明外泌体miRNA在调节炎症和免疫反应中的多效性作用及其作为硬骨鱼生物标志物的潜在用途。
Exosomes are a class of extracellular vesicles with diameters ranging from ~50 to 150 nm. Incorporating diverse biological substances and being present extensively in biofluids, exosomes are involved in intracellular communication in various physiological and pathological processes and emerging as promising biomarkers for the prognosis and diagnosis of many diseases. Accumulating evidence shows that exosomes also play important roles in the inflammatory and immune responses to bacterial infection. However, the study of exosomes in teleost fish remains scarce. In the present study, we focused on the exosomal microRNAs (miRNAs) in the plasma of Chinese tongue sole (Cynoglossus semilaevis) in response to Vibrio harveyi infection. After bacterial challenge, the plasma was sampled at both the early (6 and 16 h) and late stages. (48, 72, and 96 h) of infection, followed by exosome isolation and exosomal miRNA sequencing. Results showed that the expression profile of 85 exosomal miRNAs was significantly different among the control, early-, and late-infection groups. The predictive genes targeted by exosomal miRNAs were extensively involved in various inflammatory and immune processes by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, suggesting that a series of processes were regulated by exosomal miRNAs in the plasma, including the pathogen invasion and recognition and the activation and regulation of signaling pathways related to cytokine production. Moreover, the spleen was found to be a preference for exosome enrichment and the underlying mechanism of interleukin-6 production regulated by ZC3H12A, ARID5A, and exosomal ssa-miR-146a-5p were probably present in Chinese tongue sole. Additionally, the enhanced levels of ssa-miR-146a-5p and nbr-miR-731 in plasma exosomes and the spleen of the infection groups were identified, indicating their application as biomarkers in favor of the prognosis and diagnosis of V. harveyi infection in Chinese tongue sole. Therefore, the collective results in the present study indicated the pleiotropic roles of exosomal miRNAs in the regulation of inflammatory and immune responses and their potential utilization as biomarkers in teleost fish.
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