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.