Hepatitis C virus core protein induces activation of hepatic stellate cell by down-regulation of silent information regulator 1

Abstract

Abstract: Objective To investigate the effects of hepatitis C virus (HCV) core protein on expression of silent information regulator 1 (SIRT1) and activation of hepatic stellate cells (HSC). Methods HSC (LX-2 cells) were co-cultured with HepG2 cells or HCV core protein-positive HepG2 cells. Activity, mRNA and protein expressions of SIRT1 in LX-2 cells were detected using scintillation counter, real time-PCR (RT-PCR) and western blot, respectively. Expressions of phosphorylated adenosine monophosphate activated protein kinase (p-AMPK), adiponectin receptor 2 (AdipoR2) and transforming growth factor β1 (TGF-β1) were measured using western blot. Levels of collagen Ⅳ (ColⅣ), procollagen Ⅲ peptide (PⅢNP), hyaluronan (HA) and laminin (LN) in the supernatant were measured using enzyme-linked immunosorbent assay (ELISA). The quantitative data was analyzed using t-test.Results Compared with LX-2 cells co-cultured with HepG2 cells, the activity (0.4±0.1 vs. 1.0±0.2, t=6.573, P<0.01), mRNA (0.3±0.1 vs. 1.0±0.3, t=5.422, P<0.01) and protein expressions (0.4±0.1 vs. 0.8±0.2, t=4.382, P<0.01) of SIRT1 were both reduced in LX-2 cells co-cultured with HCV core-positive HepG2 cells. In LX-2 cells co-cultured with HCV core-positive HepG2 cells, the expression levels of p-AMPK protein (0.3±0.1 vs. 0.8±0.2, t=5.477, P<0.01) and AdipoR2 protein (0.4±0.1 vs. 0.8±0.2, t=4.382, P<0.01) were decreased comparing with those in LX-2 cells co-cultured with HepG2 cells, while TGF-β1 protein expression (2.3±0.5 vs 0.8±0.2, t=6.823, P<0.01) was increased. Moreover, the levels of ColⅣ, PⅢNP, HA and LN in the supernatant were increased in LX-2 cells co-cultured with HCV core-positive HepG2 cells. SIRT1 activator resveratrol decreased the expression of TGF-β1 protein.Conclusion HCV core protein might decrease the expression of AdipoR2 and increase the expression of TGF-β1 through down-regulating the activity and expression of SIRT1, and ultimately cause the activation of HSC.

Key words: Hepatitis C virus, Core protein, Silent information regulator 1, Hepatic stellate cells, Adiponectin receptor

SUN Li-jie, SHI Yu-guang, ZHANG Xiao-yu, SHU Meng-ni, CHEN Mo-yang, YU Jian-wu.. Hepatitis C virus core protein induces activation of hepatic stellate cell by down-regulation of silent information regulator 1[J]. Chinese Hepatolgy, 2017, 22(7): 602-604.

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