HBxAg suppresses cell apoptosis and promotes the secretion of placental hormones in human placental trophoblasts via activation of the EGFR/Akt pathway.

The aim of this study is to investigate the role of Hepatitis B virus x (HBx) in the growth and secretion of human placental trophoblasts. Firstly, placenta tissues were collected from pregnant HBV carriers with various viral loads. The results of immunohistochemical technique showed that the HBx protein and pEGFR protein levels were both markedly increased with the viral load elevation. Then, a placental trophoblast cell strain (JEG-3-HBx), which stably expressed HBx mRNA and protein, was established with the pcDNA-HBx transfection followed by the G418 selection. The JEG-3-HBx strain displayed distinct activation of the EGFR/AKT pathway, a lower level of cell apoptosis, and higher secretion levels of placental hormones, including human chorionic gonadotropin (hCG), progesterone, estrogen and β-endorphin. Subsequently, HBx siRNA was used to silence the HBx gene in the JEG-3-HBx strain. Our data showed that the HBx siRNA transfection markedly suppressed the activation of the EGFR/AKT pathway, promoted cell apoptosis, and reduced the secretion of the placental hormones. Finally, EGF was applied to simulate the JEG-3-HBx strain with or without the HBx siRNA transfection. EGF treatment counteracted the reduction of cell apoptosis and the suppression of hormone secretion caused by HBx siRNA in the cell strain. In conclusion, the pEGFR protein was robustly upregulated in HBx-infected human placenta tissues and trophoblast cells. HBx reduces cell apoptosis and promotes the secretion of placental hormones in human placental trophoblast cells via activation of the EGFR/Akt pathway.