Hepatocytes cyclooxygenase-2 deficiency improves liver injury via inhibition of endoplasmic reticulum stress and epithelial-mesenchymal transition

The mechanism underlying the loss of normal liver tissues in liver cirrhosis, mainly hepatocytes, is not well-characterized. Endoplasmic reticulum (ER) stress-induced cell death has emerged as a potential mechanism for chronic liver diseases. We have previously demonstrated that cyclooxygenase-2 (COX-2) is closely related to the progress of liver cirrhosis. In this study, we aimed to verify whether hepatocytes COX-2 deficiency could protect liver injury via inducing ER stress in liver cirrhosis. Overall design: Hepatocytes-specific COX-2 deletion mice (C57BL/6 background) were derived by breeder COX-2fl/fl mice with Alb-Cre mice. Male COX-2fl/fl/Alb-Cre+mice (COX-2 CKO) and their age-matched littermate control COX-2fl/fl/Alb-Cre- mice (WT) were used. Primary hepatocytes from COX-2 CKO or WT mice were isolated using a two-step perfusion method. For ER stress induction, cells were starved with 1% FBS for 2 hours and incubated with vehicle (DMSO) or tunicamycin (Tu, 6 µmol/L) for additional 24 hours.