Modification of endoplasmic reticulum stress expands surgical indication in hepatocellular carcinom a

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C/EBP homologous protein (CHOP) is one of the key components of the endoplasmic reticulum (ER) stress-mediated apoptosis. We investigated the role of CHOP in cholestatic liver injury. Liver fibrosis was attenuated in CHOP knockout mice after bile duct ligation (BDL). Both apoptotic and necrotic hepatocyte deaths were attenuated in CHOP deficient mice. Cholestasis induces CHOP -mediated ER stress and t riggers hepatocyte death. CHOP deficiency attenuates hepatocyte death and subsequent liver fibrosis. CHOP expression was enhanced in human liver cirrhosis and hepatocellular carcinoma. Furthermore, inhibition of c-Jun NH_2-terminal kinase switches Smad3 signaling from oncogenesis to tumor-suppression in rat hepatocellular carcinoma. Taken together, we expect that modification of ER stress expands surgical indication in hepatocellular carcinoma.