In-Depth Proteomic Analysis Reveals Phenotypic Diversity of Macrophages in Liver Fibrosis

Macrophages make up a heterogeneous population of immune cells that exhibit diverse phenotypes and functions in health and disease. Although macrophage epigenomic and transcriptomic profiles have been reported, the proteomes of distinct macrophage populations under various pathological conditions re...

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Bibliographic Details
Published in:Journal of proteome research 2024-11, Vol.23 (11), p.5166-5176
Main Authors: Yang, Wenting, Chen, Liling, Zhang, Jian, Qiu, Chenyi, Hou, Wenhao, Zhang, Xiangye, Fu, Bin, Zhao, Dianyuan, Wang, Huan, Liu, Di, Yan, Fang, Ying, Wantao, Tang, Li
Format: Article
Language:English
Subjects:
Animals
Carbon Tetrachloride - toxicity
Cell Differentiation
Kupffer Cells - metabolism
Lectins, C-Type - genetics
Lectins, C-Type - metabolism
Liver - metabolism
Liver - pathology
Liver Cirrhosis - genetics
Liver Cirrhosis - metabolism
Liver Cirrhosis - pathology
Macrophages - metabolism
Male
Mice
Mice, Inbred C57BL
Monocytes - metabolism
Monocytes - pathology
Phenotype
Proteome - analysis
Proteome - metabolism
Proteomics - methods
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Summary:Macrophages make up a heterogeneous population of immune cells that exhibit diverse phenotypes and functions in health and disease. Although macrophage epigenomic and transcriptomic profiles have been reported, the proteomes of distinct macrophage populations under various pathological conditions remain largely elusive. Here, we employed a label-free proteomic approach to characterize the diversity of the hepatic macrophage pool in an experimental model of CCl4-induced liver fibrosis. We found a decrease in the proportion of liver resident embryo-derived KCs (EmKCs), and a drastic increase in the proportion of monocyte-derived KCs (MoKCs) and CLEC2–Macs. Proteomic profiling revealed that MoKCs largely resembled EmKCs, whereas CLEC2–Macs exhibited greater proteomic alternations compared with EmKCs, suggesting two distinct destinations for monocyte differentiation during liver fibrosis. Furthermore, CLEC2–Macs were characterized by increased expression of proteins associated with inflammatory response, antigen processing and presentation processes, which may be involved in the pathogenesis of liver fibrosis. Collectively, our study provides insights into the considerable heterogeneity within the hepatic macrophage pool during liver fibrosis.
ISSN:1535-3893
1535-3907
1535-3907
DOI:10.1021/acs.jproteome.4c00681