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

C/EBP同源蛋白（CHOP）是内质网（ER）应激介导的细胞凋亡的关键成分之一。我们探讨了CHOP在胆汁淤积性肝损伤中的作用。CHOP敲除小鼠胆管结扎（BDL）后肝纤维化减轻。CHOP缺陷小鼠的凋亡和坏死肝细胞死亡均减轻。胆汁淤积诱导CHOP介导的内质网应激，并触发肝细胞死亡。CHOP缺乏可减轻肝细胞死亡和随后的肝纤维化。CHOP在人肝硬化和肝细胞癌中表达增强。此外，在大鼠肝细胞癌中，抑制c-Jun nh_2末端激酶可将Smad3信号从肿瘤发生转变为肿瘤抑制。综上所述，我们期望内质网应激的改变扩大肝细胞癌的手术指征。

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.