COVID-19 patient serum-derived extracellular vesicles deliver miR-20b-5p induces neutrophil extracellular traps.

IF 8.2 2区生物学 Q1 CELL BIOLOGY Cell Communication and Signaling Pub Date : 2025-02-17 DOI:10.1186/s12964-025-02095-1

Yao Liao, Yuheng Liu, Dinghao Li, Shiqi Luo, Yun Huang, Junwei Wu, Jin Su, Yi Yang, Ji Wu, Zifeng Zhu, Mengxi Yanglan, Haiyi Deng, Xinyi Wu, Junhao Xu, Feiyang Cao, Chunmei Cai, Zhen Li, Ruibing Yang, Xiaoyan Deng, Jie Wei, Lifu Wang

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Abstract

Background: Severe cases of COVID-19 are characterized by an excessive presence of neutrophils. Neutrophil extracellular traps (NETs), released by activated neutrophils due to SARS-CoV-2 infection, contribute to lung epithelial cell death and are key drivers in COVID-19-associated immunothrombosis. However, the mechanism underlying NET formation in COVID-19 remain unclear.

Methods: Extracellular vesicles (EVs) were isolated from the serum of COVID-19 patients and healthy volunteers, while neutrophils were isolated from blood samples of healthy volunteers. Neutrophils were treated with EVs, and the formation of NETs was observed. To identify the components responsible for the COVID-19-EVs-induced NET formation, we analyzed the expression profiles of microRNA (miRNAs) in COVID-19-EVs. We identified eight highly expressed miRNAs in COVID-19-EVs and explored their potential roles in COVID-19-EVs-mediated NET formation. Additionally, we explored the role of miR-20b-5p in COVID-19-EVs-induced NET formation.

Results: In this study, we demonstrate that patients with COVID-19 have a higher concentration of serum EVs (COVID-19-EVs) than healthy controls (Normal-EVs). We also found that COVID-19-EVs are internalized by neutrophils to induced NET formation. Through comprehensive miRNA profiling of COVID-19-EVs versus Normal-EVs, we identified 78 differentially expressed miRNAs, with 27 of these being upregulated and 51 being downregulated. Subsequently, we discovered that COVID-19-EVs that were highly abundant with certain miRNAs promote NET formation. Specifically, miR-20b-5p was found to be the strongest inducer of NET formation of the identified miRNAs. Inhibition of miR-20b-5p resulted in a significant decrease in COVID-19-EVs-mediated induction of NET formation.

Conclusion: Herein, we reveal a previously unknown role of COVID-19-EVs in NET formation, which contributes to COVID-19 progression. This study suggests that miR-20b-5p may serve as a potential therapeutic target for COVID-19 treatment.

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COVID-19 患者血清衍生的细胞外囊泡输送 miR-20b-5p 可诱导中性粒细胞细胞外捕获。

背景：COVID-19重症病例的特征是中性粒细胞过量存在。由于SARS-CoV-2感染，活化的中性粒细胞释放的中性粒细胞细胞外陷阱（NETs）有助于肺上皮细胞死亡，是covid -19相关免疫血栓形成的关键驱动因素。然而，COVID-19中NET形成的机制尚不清楚。方法：分别从COVID-19患者和健康志愿者血清中分离细胞外囊泡（EVs），从健康志愿者血液中分离中性粒细胞。用ev处理中性粒细胞，观察NETs的形成。为了确定导致covid -19- ev诱导NET形成的成分，我们分析了covid -19- ev中microRNA （mirna）的表达谱。我们在covid -19- ev中鉴定了8个高表达的mirna，并探索了它们在covid -19- ev介导的NET形成中的潜在作用。此外，我们探索了miR-20b-5p在covid -19- ev诱导的NET形成中的作用。结果：在本研究中，我们发现COVID-19患者的血清EVs （COVID-19-EVs）浓度高于健康对照组（Normal-EVs）。我们还发现covid -19- ev被中性粒细胞内化以诱导NET的形成。通过对covid -19 ev与正常ev的综合miRNA分析，我们确定了78个差异表达的miRNA，其中27个表达上调，51个表达下调。随后，我们发现富含某些mirna的covid -19- ev促进了NET的形成。具体而言，miR-20b-5p被发现是鉴定的mirna形成NET的最强诱导剂。抑制miR-20b-5p导致covid -19- ev介导的NET形成诱导显著降低。结论：本文揭示了之前未知的COVID-19- ev在NET形成中的作用，这有助于COVID-19的进展。这项研究表明，miR-20b-5p可能作为COVID-19治疗的潜在治疗靶点。

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来源期刊

Cell Communication and Signaling CELL BIOLOGY-

CiteScore

11.00

自引率

0.00%

发文量

180

期刊介绍： Cell Communication and Signaling (CCS) is a peer-reviewed, open-access scientific journal that focuses on cellular signaling pathways in both normal and pathological conditions. It publishes original research, reviews, and commentaries, welcoming studies that utilize molecular, morphological, biochemical, structural, and cell biology approaches. CCS also encourages interdisciplinary work and innovative models, including in silico, in vitro, and in vivo approaches, to facilitate investigations of cell signaling pathways, networks, and behavior. Starting from January 2019, CCS is proud to announce its affiliation with the International Cell Death Society. The journal now encourages submissions covering all aspects of cell death, including apoptotic and non-apoptotic mechanisms, cell death in model systems, autophagy, clearance of dying cells, and the immunological and pathological consequences of dying cells in the tissue microenvironment.