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

Year: 2025

Type: article

Abstract: 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. • Resveratrol exosomes deliver Snhg6, inhibiting liver fibrosis. • Snhg6 downregulates NF-κB, reducing hepatic stellate cell activation. • High Snhg6 in exosomes contrasts with low levels in fibrotic serum. • Silencing Snhg6 confirms its role in anti-fibrotic pathways. • Animal models show resveratrol exosomes mitigate liver fibrosis.

Source: Genomics

DOI: 10.1016/j.ygeno.2025.111043