Exosomes derived from natural killer cells inhibit hepatic stellate cell activation and liver fibrosis

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.