Role of JNK in Restoration and Regeneration Phase
Proliferation and recovery of cells are extremely important after APAP-induced cell death. Inhibition of EGFR in liver cells, 12 hours after APAP injection, leads to impairment in proliferation, persistence of liver injury and an increase in mouse mortality [153]. JNK plays an important role in cell proliferation [59]. Therefore, knockout of JNK1 inhibits progression of liver cancer and proliferation of hepatocytes is significantly affected. In addition, JNK1 is involved in transformation of hepatic stellate cells into fibroblasts. Notably, inhibition of JNK attenuates fibrosis in models of bile duct ligation or CCl4-induced liver injury [154]. Therefore, JNK may promote regeneration of liver cells during the late stages of APAP-induced liver injury and protect liver cells against APAP hepatotoxicity. Furthermore, recent studies report that JNK may be critical to cell survival [155] because JNK promotes recovery and regeneration of liver cells after APAP-induced death of liver cells. Additionally, silencing CHOP, which is a downstream gene of JNK, promotes proliferation of hepatocytes during APAP-induced liver injury [117]. However, further studies should explore the role of JNK in recovery and regeneration of cells following APAP-induced liver injury.