Hepatitis C virus core protein induces dysfunction of liver sinusoidal endothelial cell by down-regulation of silent information regulator
SUN Li-jie, SHI Yu-guang, ZHANG Xiao-yu, SHU Meng-ni, CHEN Mo-yang, YU Jian-wu.
2017, 22(8):
690-694.
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Objective To investigate the effect of hepatitis C virus (HCV) core protein on expression of silent information regulator 1 (SIRT1) and function of liver sinusoidal endothelial cell (LSEC).Methods LSEC was co-cultured with HepG2 cells with/without expressing HCV core protein, respectively. After co-culture, the activity and expression levels of SIRT1 in LSEC were detected by scintillation counter in mRNA and protein levels, using real-time polymerase chain reaction (RT-PCR) and western blot, respectively. Levels of adiponectin receptor 2 (AdipoR2), endothelial nitric oxide synthase (eNOS), von Willebrand factor (vWf), cluster of differentiation (CD) 31, vascular endothelial growth factor (VEGF) and CD14 were measured using western blot. Level of reactive oxygen species (ROS) was assayed using flow cytometry. Levels of malondialdehyde (MDA), superoxide dismutase (SOD), adiponectin, nitric oxide (NO) and endothelin-1 (ET-1) in the supernatant were measured. The quantitative data was analyzed using t-test.Results Compared with co-culture cells without expressing HCV core protein, the co-culture cells with expressing HCV core protein showed lower activity (0.3±0.1 vs 1.0±0.3, t=5.422, P<0.01), mRNA (0.4±0.1 vs 1.0±0.2, t=6.573, P<0.01) and protein (0.3±0.08 vs 1.0±0.3, t=5.613, P<0.01) of SIRT1; vWf protein (0.8±0.3 vs 0.4±0.1, t=3.098, P<0.01), CD31 protein (0.9±0.2 vs 0.3±0.1, t=6.573, P<0.01) and VEGF protein (0.9±0.3 vs 0.5±0.1, t=3.873, P<0.01); lower levels of adiponectin (3.41±0.61 vs 5.82±0.87μg/mL, t=5.556, P<0.01), AdipoR2 protein (0.3±0.1 vs 0.8±0.2, t=5.477, P<0.01), eNOS protein (0.4±0.1 vs 0.9±0.3, t=3.873, P<0.01) and CD14 protein (0.4±0.1 vs 0.9±0.3, t=3.873, P<0.01), respectively. Additionally, compared to those in the supernatant of co-culture cells without expressing HCV core protein, NO and SOD levels were decreased in co-culture cells with expressing HCV core protein, whereas ET-1 and MDA levels were increased.Conclusion HCV core protein may down-regulate the activity and expression of SIRT1, decrease adiponectin and AdipoR2, subsequently induce LSEC contraction and hepatic sinusoidal capillarization, as well as increase oxidative stress, ultimately lead to liver microcirculation disturbance.
