Exosome Carrying OCT4/miR-1246/β-catenin Deriving From HBV Infected Hepatocytes Accelerated Liver Fibrosis

Area of Science:

• Hepatology
• Molecular Biology
• Virology

Background:

• Octamer-binding transcription factor 4 (OCT4) is implicated in liver fibrosis (LF) development.
• The precise mechanism linking OCT4 to hepatitis B virus (HBV)-associated LF requires elucidation.

Purpose of the Study:

• To investigate the mechanistic role of OCT4 in HBV-associated LF.
• To explore the involvement of the OCT4/miR-1246/β-catenin pathway in HBV-induced liver fibrosis.

Main Methods:

• Utilized HepAD38 and HepG2-NTCP cell lines to study HBV effects on OCT4 and miR-1246.
• Employed entecavir treatment and Hepatitis B X (HBx) knockdown to assess their impact.
• Investigated exosome-mediated transfer of fibrogenic factors.
• Analyzed liver tissue from 26 HBV-infected patients.

Main Results:

• HBV infection significantly increased OCT4 and miR-1246 expression, which was reversed by entecavir or HBx knockdown.
• OCT4 overexpression boosted miR-1246, β-catenin, and LF-associated genes in hepatic stellate cells.
• Exosomes from HBV-infected cells promoted fibrogenesis in hepatic stellate cells via the OCT4/miR-1246/β-catenin pathway.
• miR-1246 and β-catenin levels in patient liver tissue correlated strongly with LF severity.

Conclusions:

• HBV induces liver fibrosis through an exosomal pathway involving OCT4, miR-1246, and β-catenin.
• This pathway represents a potential therapeutic target for treating HBV-associated liver fibrosis.