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.