Ölander Magnus, Wiśniewski Jacek R, Artursson Per
Department of Pharmacy, Uppsala University, Uppsala, Sweden.
Biochemical Proteomics Group, Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
Liver Int. 2020 Jul;40(7):1770-1780. doi: 10.1111/liv.14452. Epub 2020 Apr 12.
BACKGROUND & AIMS: The human liver functions through a complex interplay between parenchymal and non-parenchymal cells. Mass spectrometry-based proteomic analysis of intact tissue has provided an in-depth view of the human liver proteome. However, the predominance of parenchymal cells (hepatocytes) means that the total tissue proteome mainly reflects hepatocyte expression. Here we therefore set out to analyse the proteomes of the major parenchymal and non-parenchymal cell types in the human liver.
We applied quantitative label-free proteomic analysis on the major cell types of the human liver: hepatocytes, liver endothelial cells, Kupffer cells and hepatic stellate cells.
We identified 9791 proteins, revealing distinct protein expression profiles across cell types, whose in vivo relevance was shown by the presence of cell-type-specific proteins. Analysis of proteins related to the immune system indicated that mechanisms of immune-mediated liver injury include the involvement of several cell types. Furthermore, in-depth investigation of proteins related to the absorption, distribution, metabolism, excretion and toxicity (ADMET) of xenobiotics showed that ADMET-related tasks are not exclusively confined to hepatocytes, and that non-parenchymal cells may contribute to drug transport and metabolism.
Overall, the data we provide constitute a unique resource for exploring the proteomes of the major types of human liver cells, which will facilitate an improved understanding of the human liver in health and disease.
人类肝脏通过实质细胞和非实质细胞之间的复杂相互作用发挥功能。基于质谱的完整组织蛋白质组学分析提供了对人类肝脏蛋白质组的深入了解。然而，实质细胞（肝细胞）占主导地位意味着总组织蛋白质组主要反映肝细胞的表达。因此，我们在此着手分析人类肝脏中主要实质细胞和非实质细胞类型的蛋白质组。
我们对人类肝脏的主要细胞类型——肝细胞、肝内皮细胞、库普弗细胞和肝星状细胞进行了无标记定量蛋白质组学分析。
我们鉴定出9791种蛋白质，揭示了不同细胞类型之间独特的蛋白质表达谱，细胞类型特异性蛋白质的存在表明了它们在体内的相关性。对与免疫系统相关蛋白质的分析表明，免疫介导的肝损伤机制涉及多种细胞类型。此外，对外源化合物的吸收、分布、代谢、排泄和毒性（ADMET）相关蛋白质的深入研究表明，ADMET相关任务并非仅局限于肝细胞，非实质细胞可能参与药物转运和代谢。
总体而言，我们提供的数据构成了探索人类肝脏主要细胞类型蛋白质组的独特资源，这将有助于更好地理解人类肝脏在健康和疾病状态下的情况。
