Hao Jun, Qi Tingting, Zhu Xiaoying, Chen Jinjun
Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, P. R. China.
Proteomics. 2020 Apr;20(8):e1900393. doi: 10.1002/pmic.201900393. Epub 2020 Apr 2.
Acute liver failure (ALF) is a severe consequence of abrupt hepatocyte injury and has lethal outcomes. Three toll-like receptor 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, tandem mass tag based quantitative proteomic analyses of three ALF mouse models are performed. 52 common differentially expressed proteins (DEPs) are identified, in three ALF groups, compared to the control. Gene ontology analyses show that among the common DEPs, ten 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 are mostly distributed in the endoplasmic reticulum and more enriched in metabolic pathways, whereas poly (I:C)/D-GalN-specific proteins are mainly in the membrane and CpG DNA/D-GalN-specific proteins are related to the ribosome structural composition. In conclusion, the common and specific DEPs in three ALF mouse models at molecular level are identified; 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.
急性肝衰竭（ALF）是肝细胞突然损伤的严重后果，具有致命结局。三种Toll样受体激动剂，包括聚肌苷酸-聚胞苷酸（poly(I:C)）、脂多糖（LPS）和胞嘧啶-磷酸-鸟嘌呤（CpG）DNA，分别在D-半乳糖胺（D-GalN）致敏的小鼠中引起急性重症肝炎。然而，三种ALF模型（LPS/D-GalN、poly(I:C)/D-GalN和CpG DNA/D-GalN）之间的分子差异尚不清楚。在此，对三种ALF小鼠模型进行了基于串联质谱标签的定量蛋白质组学分析。与对照组相比，在三个ALF组中鉴定出52种常见的差异表达蛋白（DEP）。基因本体分析表明，在常见的DEP中，有10种蛋白参与免疫系统过程，39种蛋白参与代谢过程。在poly(I:C)/D-GalN、LPS/D-GalN和CpG DNA/D-GalN组中分别有80、195和23种特异性表达蛋白，LPS/D-GalN特异性蛋白大多分布在内质网中，在代谢途径中更富集，而poly(I:C)/D-GalN特异性蛋白主要位于细胞膜，CpG DNA/D-GalN特异性蛋白与核糖体结构组成有关。总之，在分子水平上鉴定了三种ALF小鼠模型中的常见和特异性DEP；并确定了一份接近完整的小鼠肝脏蛋白质参考图谱，这将有助于人类肝衰竭的临床诊断和治疗。
