Zhang Taicheng, Jing Jie, Liang Yaodan, Luo Jianming, Cheng Dongyu, Qin Shanyu, Jiang Haixing
Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning 530021, Guangxi, China.
Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning 530021, Guangxi, China.
Genomics. 2025 May;117(3):111043. doi: 10.1016/j.ygeno.2025.111043. Epub 2025 Mar 25.
To investigate the role of lncRNA Snhg6 in liver fibrosis, delivered by resveratrol-stimulated macrophage exosomes.
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.
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.
Resveratrol-stimulated macrophage exosomes may inhibit liver fibrosis by delivering lncRNA Snhg6, which suppresses the NF-κB pathway.
研究白藜芦醇刺激的巨噬细胞外泌体所携带的长链非编码RNA Snhg6在肝纤维化中的作用。
从RAW 264.7细胞中产生白藜芦醇刺激的外泌体和未刺激的外泌体，通过电子显微镜、纳米颗粒分析和蛋白质印迹法进行确认。将JS1细胞用作肝星状细胞模型，用转化生长因子-β1激活并用外泌体处理。通过共聚焦显微镜观察外泌体摄取情况，并用免疫荧光法检测α-平滑肌肌动蛋白（acta2）表达。使用RNA测序和逆转录定量聚合酶链反应（RT-qPCR）分析外泌体长链非编码RNA谱。对差异表达基因进行京都基因与基因组百科全书（KEGG）基因集富集分析（GSEA），并使用蛋白质印迹法检测肝星状细胞中的核因子-κB（nf-κb）表达。分析肝纤维化患者血清中的SNHG6水平。
白藜芦醇刺激的外泌体抑制了转化生长因子-β1诱导的肝星状细胞激活，有132种差异表达的长链非编码RNA，包括上调的Snhg6。核因子-κB信号通路被下调。沉默Snhg6减弱了这种抑制作用。
白藜芦醇刺激的巨噬细胞外泌体可能通过传递长链非编码RNA Snhg6来抑制肝纤维化，该长链非编码RNA可抑制核因子-κB通路。
