Activation of hepatic stellate cells (HSCs) is a prominent driver of liver fibrosis. This study was designed to investigate the effect of exosomes derived from natural killer (NK) cells on HSC activation and liver fibrosis. The exosomes were isolated from NK-92MI cells (NK-Exo) and identified by transmission electron microscopy, nanoparticle tracking analysis, and western blot. Then NK-Exo was administered into TGF-β1-treated LX-2 cells (human HSC line) and mice with CCl₄-induced liver fibrosis. LX-2 cell proliferation was determined by CCK-8 assay. The levels of α-SMA and CoL1A1 were measured by qRT-PCR and western blot to evaluate HSC activation. Serum levels of AST and ALT were measured. Hematoxylin–eosin, Masson staining, and Sirius Red staining were performed to assess the pathological changes and collagen deposition. Cell supernatant derived from NK-92MI cells inhibited TGF-β1-induced HSC proliferation and activation in LX-2 cells, and this effect was counteracted by the exosome inhibitor GW4869. Further assays confirmed that NK-Exo treatment significantly inhibited TGF-β1-induced HSC proliferation and activation. Moreover, NK-Exo administration alleviated CCl₄-induced liver fibrosis in mice. NK-Exo inhibited TGF-β1-induced HSC activation and CCl₄-induced liver fibrosis.

中文翻译：

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源自自然杀伤细胞的外泌体抑制肝星状细胞活化和肝纤维化。

肝星状细胞 (HSC) 的激活是肝纤维化的重要驱动因素。本研究旨在研究源自自然杀伤 (NK) 细胞的外泌体对 HSC 活化和肝纤维化的影响。外泌体从 NK-92MI 细胞 (NK-Exo) 中分离出来，并通过透射电子显微镜、纳米粒子追踪分析和蛋白质印迹进行鉴定。然后将 NK-Exo 施用于 TGF-β1 处理的 LX-2 细胞（人 HSC 系）和具有 CCl _4的小鼠- 诱发肝纤维化。LX-2细胞增殖通过CCK-8测定法确定。通过qRT-PCR和蛋白质印迹测量α-SMA和CoL1A1的水平以评估HSC活化。测定血清AST和ALT水平。进行苏木精-伊红染色、马松染色和天狼星红染色以评估病理变化和胶原沉积。源自 NK-92MI 细胞的细胞上清液抑制 LX-2 细胞中 TGF-β1 诱导的 HSC 增殖和活化，而这种作用被外泌体抑制剂 GW4869 抵消。进一步的测定证实，NK-Exo 治疗显着抑制了 TGF-β1 诱导的 HSC 增殖和活化。此外，NK-Exo 给药减轻了 CCl ₄诱导的小鼠肝纤维化。NK-Exo 抑制 TGF-β1 诱导的 HSC 活化和 CCl ₄- 诱发肝纤维化。