Xue Fan , Qianhui Tang , Ninglin Xia , Jiwei Wang , Wen Zhao , Ming Jin , Qian Lu , Jinyu Hu , Rongmi Zhang , Luyong Zhang , Zhenzhou Jiang , Qinwei Yu
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引用次数: 0
Abstract
Introduction
Liver fibrosis is a common pathological process in chronic liver disease, reflecting the advanced stage of the disease. Liver endothelial cells (ECs), especially liver sinusoidal endothelial cells (LSECs), are recognized as critical modulators of liver homeostasis and play essential roles in the recruitment and function of liver immune cells. In this study, we aimed to explore the mechanism of hepatic EC injury and the potential regulatory pathways of intercellular communication in liver fibrosis.
Methods
In this study, C57BL/6 male mice were treated with CCl4 for 6 weeks to establish a liver fibrosis model. Masson staining and immunohistochemistry were performed to assess the extent of liver fibrosis. Hepatic endothelial injury was detected by using scanning electron microscopy (SEM) and PCR technology. Single-cell RNA sequencing (scRNA-seq) was performed to analyze phenotypic changes in nonparenchymal cells and dissect intercellular crosstalk.
Results
A total of 24,534 cells were clustered into 10 main cell subsets. The LSEC fenestrae and surface receptor expression were reduced, and the expression of Cd34 was upregulated. Liver ECs exhibited dense cellular crosstalk with immune cells (macrophages, T and B cells). The analysis of intercellular signaling pathways revealed that immune cells targeted liver ECs through the Ptprc-Mrc1 and Sell-Podxl signaling pathways to maintain cellular interactions during liver fibrosis.
Conclusion
We revealed apparent damage and capillarization of liver ECs and demonstrated the cell-cell communications among liver immune cells and ECs during the development of liver fibrosis. The Ptprc-Mrc1 and Sell-Podxl signaling pathways exerted prominent roles in liver immune cell-EC interactions.
期刊介绍:
The European Journal of Pharmacology publishes research papers covering all aspects of experimental pharmacology with focus on the mechanism of action of structurally identified compounds affecting biological systems.
The scope includes:
Behavioural pharmacology
Neuropharmacology and analgesia
Cardiovascular pharmacology
Pulmonary, gastrointestinal and urogenital pharmacology
Endocrine pharmacology
Immunopharmacology and inflammation
Molecular and cellular pharmacology
Regenerative pharmacology
Biologicals and biotherapeutics
Translational pharmacology
Nutriceutical pharmacology.