白藜芦醇刺激巨噬细胞外泌体传递lncRNA Snhg6通过调节NF-κB途径抑制肝纤维化

IF 3 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Genomics Pub Date : 2025-03-25 DOI:10.1016/j.ygeno.2025.111043

Taicheng Zhang , Jie Jing , Yaodan Liang , Jianming Luo, Dongyu Cheng, Shanyu Qin, Haixing Jiang

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引用次数: 0

摘要

目的探讨lncRNA Snhg6在白藜芦醇刺激巨噬细胞外泌体介导肝纤维化中的作用。方法制备白藜芦醇刺激和非刺激的外泌体，并通过电镜、纳米颗粒分析和Western blotting进行验证。以JS1细胞作为HSC模型，用TGF-β1激活，外泌体处理。共聚焦显微镜观察外泌体摄取，免疫荧光法检测acta2表达。采用RNA测序和RT-qPCR分析外泌体lncRNA谱。对差异表达基因进行KEGG - GSEA富集，用WB检测造血干细胞中nf-κb的表达。分析肝纤维化患者血清中SNHG6水平。结果白藜芦醇刺激的外泌体抑制TGF-β1诱导的HSC活化，有132种不同表达的lncrna，包括上调的Snhg6。NF-κB信号下调。沉默Snhg6减弱了这种抑制作用。结论白藜芦醇刺激的巨噬细胞外泌体可能通过传递lncRNA Snhg6抑制NF-κB通路抑制肝纤维化。

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Resveratrol-stimulated macrophage exosomes delivering lncRNA Snhg6 inhibit liver fibrosis by modulating the NF-κB pathway

Objective

To investigate the role of lncRNA Snhg6 in liver fibrosis, delivered by resveratrol-stimulated macrophage exosomes.

Methods

Resveratrol-stimulated and unstimulated exosomes were generated from RAW 264.7 cells, confirmed by electron microscopy, nanoparticle analysis, and Western blotting. JS1 cells were used as an HSC model, activated with TGF-β1 and treated with exosomes. Exosome uptake was observed via confocal microscopy, and acta2 expression was measured with immunofluorescence. RNA sequencing and RT-qPCR were used to analyze exosomal lncRNA profiles. KEGG GSEA enrichment was conducted on differentially expressed genes, and nf-κb expression was detected in HSCs using WB. Serum from liver fibrosis patients was analyzed for SNHG6 levels.

Results

Resveratrol-stimulated exosomes inhibited TGF-β1-induced HSC activation, with 132 differentially expressed lncRNAs, including upregulated Snhg6. NF-κB signaling was downregulated. Silencing Snhg6 weakened this inhibitory effect.

Conclusion

Resveratrol-stimulated macrophage exosomes may inhibit liver fibrosis by delivering lncRNA Snhg6, which suppresses the NF-κB pathway.

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来源期刊

Genomics 生物-生物工程与应用微生物

CiteScore

9.60

自引率

2.30%

发文量

260

审稿时长

60 days

期刊介绍： Genomics is a forum for describing the development of genome-scale technologies and their application to all areas of biological investigation. As a journal that has evolved with the field that carries its name, Genomics focuses on the development and application of cutting-edge methods, addressing fundamental questions with potential interest to a wide audience. Our aim is to publish the highest quality research and to provide authors with rapid, fair and accurate review and publication of manuscripts falling within our scope.