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

Accumulating research highlights the critical involvement of octamer‐binding transcription factor 4 (OCT4) in liver fibrosis (LF) development. However, the mechanistic relationship between OCT4 and hepatitis B virus (HBV)‐associated LF remains unclear. HBV exposure markedly upregulated OCT4 and miR‐1246 expression in both HepAD38 and HepG2‐NTCP cell lines. These effects were reversed by entecavir treatment or the Hepatitis B X (HBx) knockdown. Furthermore, overexpression of OCT4 enhanced expression of miR‐1246, β‐catenin, and LF‐associated genes in LX2 (Hepatic stellate cell) cells. Interestingly, exosomes from HBV infected HepG2‐NTCP cells upregulated OCT4/miR‐1246/β‐catenin expression as well as α‐SMA, Col1A and TIMP‐1 in LX2 cells. These fibrogenic effects were inhibited by HBx gRNA. Moreover, 26 HBV infected patients were enrolled in this study. The expression of miR‐1246 and β‐catenin in liver tissue were strongly correlated with LF. These results showed that HBV induced LF through exosomal OCT4/miR‐1246/β‐catenin Pathway, which lay a basis for LF treatment.