Comparative liver proteomic analysis of protein expression changes in an acute-on-chronic liver failure mouse model

Purpose: Acute-on-chronic liver failure (ACLF) is a major cause of mortality and morbidity owing to the lack of targeted therapeutic interventions. The molecular mechanisms underlying the complex pathogenesis of ACLF are still unclear. Therefore, in this study, we established an ACLF mouse model using a combination of carbon tetrachloride (CCl 4 ) with lipopolysaccharide (LPS) and D-galactosamine (D-Gal) (CCl 4 + LPS/D-Gal) via intraperitoneal administration. Moreover, the underlying molecular pathogenesis of ACLF was explored. Methods: Four-dimensional label-free mass spectrometry-based quantitative proteomics was used to identify liver proteins that were differentially expressed in liver samples from CCl 4 + LPS/D-Gal-induced ACLF mouse liver samples. Results: Approximately 258, 380, and 471 proteins with a minimum mean expression fold change of 2 were differentially expressed in the liver fibrosis (LF), liver cirrhosis (LC), and ACLF groups, respectively, compared with those in the control (CTRL) group. Furthermore, the mice ACLF showed increased myeloperoxidase (MPO) and coronin-1A (CORO1A) levels, consistent with the phagosome pathway. These two proteins were potential targets for regulating the clinical features and progression of liver injury in ACLF mice. Conclusion: To the best of our knowledge, we are the first to provide a global differential protein expression profile of CCl 4 + LPS/D-Gal-induced ACLF mouse liver samples using label-free mass spectrometry-based quantitative proteomics. Overall, molecular differences in ACLF regulated the phagosome pathway at different disease stages, clarifying ACLF pathogenesis. MPO and CORO1A are the underlying predictors of ACLF severity or prognosis, and their regulation may facilitate timely and intensive clinical intervention.