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• W3060285770 startingPage "110586" @default.
• W3060285770 abstract "Sphingosine kinase 1 (SphK1) plays critical roles in the activation of hepatic stellate cells (HSCs) and liver fibrosis. Our previous study found that polydatin ameliorates chronic liver injury and fibrosis by inhibiting oxidative stress. However, whether polydatin exerts an anti-fibrotic effect on liver fibrosis dependent on SphK1 signaling is unknown. We aimed to investigate the role of polydatin in SphK1, which mediates HSC activation and liver fibrosis. C57BL/6 mice were induced using CCl4 5 μL g−1 i.p. twice a week for 6 weeks and treated with or without polydatin. Human immortalized HSC line (LX-2) was induced using platelet-derived growth factor-BB (PDGF-BB) or adenovirus-SphK1 and treated with polydatin. Hepatic macrophage filtration, collagen deposition, expression of α-smooth muscle, active caspase-3, and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells were markedly increased in mice induced by CCl4 for 6 weeks. In contrast, polydatin attenuated collagen synthesis and hepatocyte apoptosis. Furthermore, polydatin exhibited significant anti-proliferative activity against PDGF-BB-induced activated hepatic stellate cells (HSCs). SphK1 was strongly induced in mice exposed to CCl4, whereas its expression and activity were inhibited by polydatin treatment. Finally, SphK1 overexpression in LX-2 cells promoted proliferation of activated HSCs, which could not be reversed by polydatin treatment. These results demonstrate that polydatin attenuates HSC proliferation and activation through inhibition of SphK1 signaling, contributing to the suppression of liver fibrosis." @default.
• W3060285770 created "2020-08-24" @default.
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• W3060285770 date "2020-10-01" @default.
• W3060285770 modified "2023-10-09" @default.
• W3060285770 title "Polydatin attenuates hepatic stellate cell proliferation and liver fibrosis by suppressing sphingosine kinase 1" @default.
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• W3060285770 doi "https://doi.org/10.1016/j.biopha.2020.110586" @default.
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