Comparative proteomic analyses of the liver in D-galactosamine sensitized mice treated with different toll-like receptor agonists

ABSTRACT: Acute liver failure (ALF) is a severe consequence of abrupt hepatocyte injury with lethal outcomes. Three toll-like receptor (TLR) agonists, including polyinosinic-polycytidylic acid [poly(I:C)], lipopolysaccharide (LPS), and cytosine-phosphate-guanine oligonucleotide (CpG ODN), respectively, cause severe and acute hepatitis in D-galactosamine (D-GalN) sensitized mice as the experimental ALF animal models. However, the molecular differences in ALF among the three models are unclear. Here, we conducted global proteomic analyses of the three ALF mice models. We identified 227, 321, and 114 differentially regulated proteins and 80,195, and 23 specifically expressed proteins in the poly(I:C)/D-GalN, LPS/D-GalN and CpG ODN/D-GalN groups compared to the control group, respectively. Fifty-two proteins were commonly identified in the three ALF groups. Gene ontology (GO) analyses showed that 45 proteins were located in organelles, 35 proteins were involved in metabolic processes, and 10 proteins were involved in immune system processes. Poly (I:C)- and LPS-specific proteins were mainly distributed in the membrane and endoplasmic reticulum, respectively. LPS-specific proteins were more enriched in metabolic pathways. CpG-specific proteins were mainly related to the ribosome structural composition. In conclusion, our study shows different molecular mechanisms of three TLR agonists in D-GalN induced ALF and provides a useful dataset for the guidance of future studies.

ORGANISM(S): Mus Musculus

SUBMITTER: Jinjun Chen  

PROVIDER: PXD017180 | iProX | Sun Jan 19 00:00:00 GMT 2020

REPOSITORIES: iProX