Abstract

Chemokine receptors are members of the G protein-coupled receptor superfamily, which together with chemokine ligands form chemokine networks to regulate various cellular functions, immune and physiological processes. These receptors are closely related to cell movement and thus play a vital role in several physiological and pathological processes that require regulation of cell migration. CXCR4, one of the most intensively studied chemokine receptors, is involved in many functions in addition to immune cells recruitment and plays a pivotal role in the pathogenesis of liver disease. Aberrant CXCR4 expression pattern is related to the migration and movement of liver specific cells in liver disease through its cross-talk with a variety of significant cell signaling pathways. An in-depth understanding of CXCR4-mediated signaling pathway and its role in liver disease is critical to identifying potential therapeutic strategies. Current therapeutic strategies for liver disease mainly focus on regulating the key functions of specific cells in the liver, in which the CXCR4 pathway plays a crucial role. Multiple challenges remain to be overcome in order to more effectively target CXCR4 pathway and identify novel combination therapies with existing strategies. This review emphasizes the role of CXCR4 and its important cell signaling pathways in the pathogenesis of liver disease and summarizes the targeted therapeutic studies conducted to date.

Highlights

  • Liver disease is a leading cause of illness and death in the world (Wang et al, 2014; Marcellin and Kutala, 2018)

  • This review aims to provide a comprehensive overview of the role of CXCR4 and its ligand in liver disease, including its potential as a therapeutic target, and summarize the therapeutic studies of combined targeting CXCR4 pathway

  • There is strong evidence that CXCR4 and its ligand play a key role in multiple liver diseases such as hepatitis, liver injury and regeneration, liver fibrosis and cirrhosis, as well as in hepatocellular carcinoma (HCC)

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Summary

Introduction

Liver disease is a leading cause of illness and death in the world (Wang et al, 2014; Marcellin and Kutala, 2018). Because the molecular mechanism of liver disease is very complicated, there is still no clinically effective treatment for specific pathogenesis. The current academic opinion holds that specific cells in the liver play a significant role in the pathophysiology of liver disease (Poisson et al, 2017; Cai B. et al, 2020). How these cells play a role in liver disease, and the specific molecular mechanisms that regulate cellular functions are still not fully elucidated.

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