Hepatitis B virus directly promotes collagen I expression of LX-2 cells without infection in vitro

Aim: To investigate direct effects of hepatitis B virus (HBV) on collagen type I in vitro. Methods: Collagen type I were measured after LX‐2 cell cultured with purified or serum HBV for 12, 24 and 48 h. Furthermore, evidence of HBV infection to LX‐2 were detected, and different inhibitors were used to identify pathways regulating collagen I expression. Results: The 3 × 10⁵ IU/mL purified/serum HBV increased collagen type I mRNA expression by 2.2‐/3.2‐ and 1.3‐/1.5‐fold at 24 and 48 h, respectively. Collagen type I protein in the supernatant of purified/serum HBV group also increased compared to the control group (408.0 ± 8.0/384.4 ± 6.8 vs 262.7 ± 15.7 ng/mL, P < 0.05). However, the 3 × 10⁷ IU/mL purified/serum HBV increased collagen type I expression similar to that of 3 × 10⁵ IU/mL, while 3 × 10³ IU/mL group showed no effect. Human HBV immunoglobulin alleviated HBV‐induced collagen I expression, but no evidence of HBV infection was found. Neutralization of transforming growth factor beta, tumor necrosis factor alpha, platelet‐derived growth factor, extracellular signal‐regulated kinase and TGF‐β receptor had no obvious inhibitory effects; only inhibition of p38 mitogen‐activated protein kinase decreased collagen type I mRNA expression by 0.5‐/0.4‐ and 0.4‐/0.3‐fold at 24 and 48 h, respectively. It reduced collagen type I protein in the purified/serum HBV group for 48 h (252.1 ± 14.1/251.7 ± 18.8 vs 403.9 ± 4.9/385.0 ± 4.2 ng/mL, P < 0.05). Conclusion: HBV directly promotes collagen type I expression of LX‐2 cells without infection in vitro.