Abstract
BACKGROUND AND AIMS: Cell-cycle-related and expression elevated protein in tumor (CREPT, also named RPRD1B) is highly expressed in tumors and functions to promote tumorigenesis. However, the role of CREPT in the pathophysiology of acute liver injury is limited. Here, we demonstrate that CREPT plays an essential role during acute liver injury. APPROACH AND RESULTS: Hepatocyte-specific CREPT knockout (CREPT(hep-/-)) and CREPT(flox/flox) mice were generated and subjected to the CCl(4) challenge for the acute (24 h) liver injury. The acute CCl(4) challenge triggered increased inflammation as well as liver injury, associated with stronger apoptotic and necroptotic cell death in CREPT(hep-/-) mice. CREPT knockout down-regulated the expression of different genes involved in cell survival, inflammation and fibrosis under acute CCl(4) challenge conditions. Antioxidant enzymes such as superoxide dismutase 2 (Sod2) and ferritin heavy chain 1 (Fth1) are dramatically induced at 24 h post-CCl(4) treatment, but this induction is blocked by transcriptional inactivation of NF-κB/Nrf2, indicating that CREPT might promote hepatocyte survival in acute liver injury by participating in the transactivation of antioxidant genes. CONCLUSIONS: These results elucidate the role of CREPT in acute liver injury and provide hints for future research on how CREPT might function in hepatocyte renewal.