Hepatitis B virus X protein maintains hepatic stellate cell activation by regulating peroxisome proliferator-activated receptor Y

Background: Chronic hepatitis B virus (HBV) infection is a major cause of hepatic fibrosis, and the activation of hepatic stellate cells (HSCs) is the main mechanism of fibrosis. However, the mechanism of hepatic fibrosis induced by HBV is not well elucidated. Hepatitis B virus X protein (HBx), one of the HBV-related proteins, induces fibrosis in a paracrine way. Peroxisome proliferator-activated receptor y (PPARy) inhibits the activation of HSCs and even switches the cell phenotype from activated to quiescent. The aim of this study was to determine the interaction of HBx and PPARy in stellate cell activation. Methods: A stable cell line, LX-2-X, which expressed HBx, was established by infecting LX-2 cells with lentivirus. The Cell Counting Kit-8 (CCK-8) assay was used to detect cell proliferation. The expression of PPARy, transforming growth factor-beta 1 (TGF beta 1), alpha-smooth muscle actin (alpha-SMA) and collagen I was measured by quantitative real-time PCR (qRT-PCR), Western blot or ELISA. For the interaction of HBx and PPARy, co-immunoprecipitation and luciferase reporter assays were performed. Results: LX-2-X cells showed increased proliferation compared to control cells, and the PPARy ligand troglitazone (0, 5, 10 mu mol/L) inhibited LX-2-X cell proliferation in a dose-dependent manner. The expression of TGF-beta 1, alpha-SMA, and collagen I increased, while PPARy decreased in LX-2-X cells. HBx bound to PPARy and suppressed the transcriptional activity of PPARy. Conclusions: HBx can maintain stellate cell activation by down-regulating PPARy in vitro.