Hepatitis B virus/hepatitis C virus upregulate angiopoietin-2 expression through mitogen-activated protein kinase pathway.

Aim: To explore the molecular mechanism of hepatitis B virus (HBV)/hepatitis C virus (HCV) upregulate angiopoietin-2 (Ang-2) expression. Methods: Reverse transcription polymerase chain reaction (RT-PCR), quantitative real-time (qRT)-PCR and enzyme-linked immunosorbent assay (ELISA) analysis were used to measure the Ang-2 transcription and expression level. Reporter gene assays were used to determine the cis-element of the Ang-2 promoter. The specific inhibitors assay, immunofluorescence and western blot analysis were conducted to verify the signal pathway involved in the upregulation of Ang-2 expression. Results: The level of transcription and expression of Ang-2 increased in the HepG2.2.15 and Con-1 cells. Reporter gene assays in HepG2.2.15 and Con-1 cells revealed that HBV/HCV could enhance Ang-2 promoter expression by activating AP-1 and Ets1. Analysis with specific inhibitors indicated that HBV/HCV upregulated the expression of Ang-2 through mitogen-activated protein kinase (MAPK) pathways. Conclusion: This study illustrates a distinct mechanism by which a tumor virus modulates vasculature to promote tumorigenesis.