NF-κB-induced gp96 up-regulation promotes hepatocyte growth，cell cycle progression and transition

Abstract:

Abstract:［Objective］To investigate the mechanism of gp96 raised during hepatitis B virus (HBV) infection and the pathological mechanism． ［Methods］ The mechanism of NF-κB activating gp96 expression was determined by bioinformatics analysis，luciferase reporter assay，real-time PCＲ and Western blot．The effect of over-expression and knockdown gp96 expression by transfection or ＲNA interference on hepatocyte proliferation，apoptosis and cell cycle was examined by CCK-8 and flow cytometry．The role of gp96 for HCC development was determined by epithelial-mesenchymal transition (EMT) and colony formation assay．［Results］NF-kB significantly increased the gp96 expression by binding to the NF-kB binding site．Over-expression and knockdown studies both show that gp96 promoted hepatocyte proliferation，inhibited apoptosis，and induced G0/G1 to S phase cell cycle progression．Moreover，gp96 induced epithelialmesenchymal transition and increased colony formation ability of hepatocytes．［Conclusion］Our results therefore provide insights in chronic HBV infection-induced gp96 expression，and indicate that elevated gp96 may contribute to HCC development during chronic inflammation．