Acute liver failure (ALF) is a severe consequence of abrupt hepatocyte injury and has lethal outcomes. Three Toll-like receptor (TLR) agonists, including polyinosinic-polycytidylic acid [poly(I:C)], lipopolysaccharide (LPS) and cytosine-phosphate-guanine (CpG) DNA, cause acute and severe hepatitis, respectively, in D-galactosamine (D-GalN)-sensitized mice. However, the molecular differences among three ALF models [LPS/D-GalN, poly(I:C)/D-GalN, and CpG DNA/D-GalN], are unclear. Here, we performed Tandem mass tag (TMT)-based quantitative proteomic analyses of three ALF mouse models. We identified 52 common differentially expressed proteins (DEPs), in three ALF groups, compared to the control. Gene ontology (GO) analyses showed that among the common DEPs, 10 proteins are involved in immune system process, and 39 proteins in metabolic process. Among 80,195 and 23 specifically expressed proteins in poly(I:C)/D-GalN, LPS/D-GalN and CpG DNA/D-GalN groups, LPS/D-GalN-specific proteins were mostly distributed in the endoplasmic reticulum and more enriched in metabolic pathways, whereas poly (I:C)/D-GalN-specific proteins were mainly in the membrane and CpG DNA/D-GalN-specific proteins were related to the ribosome structural composition. In conclusion, we identified common and specific DEPs in three ALF mouse models at molecular level; and determined a close-to-complete reference map of mouse liver proteins which will be useful for clinical diagnosis and treatment of liver failure in humans. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.