Abstract
Macrophages are important immune cells in innate immunity, and have remarkable heterogeneity and polarization. Under pathological conditions, in addition to the resident macrophages, other macrophages are also recruited to the diseased tissues, and polarize to various phenotypes (mainly M1 and M2) under the stimulation of various factors in the microenvironment, thus playing different roles and functions. Liver diseases are hepatic pathological changes caused by a variety of pathogenic factors (viruses, alcohol, drugs, etc.), including acute liver injury, viral hepatitis, alcoholic liver disease, metabolic-associated fatty liver disease, liver fibrosis, and hepatocellular carcinoma. Recent studies have shown that macrophage polarization plays an important role in the initiation and development of liver diseases. However, because both macrophage polarization and the pathogenesis of liver diseases are complex, the role and mechanism of macrophage polarization in liver diseases need to be further clarified. Therefore, the origin of hepatic macrophages, and the phenotypes and mechanisms of macrophage polarization are reviewed first in this paper. It is found that macrophage polarization involves several molecular mechanisms, mainly including TLR4/NF-κB, JAK/STATs, TGF-β/Smads, PPARγ, Notch, and miRNA signaling pathways. In addition, this paper also expounds the role and mechanism of macrophage polarization in various liver diseases, which aims to provide references for further research of macrophage polarization in liver diseases, contributing to the therapeutic strategy of ameliorating liver diseases by modulating macrophage polarization.
Highlights
The liver is an essential organ for maintaining normal life activities of the human body, because it regulates the metabolism of many nutrients and chemical drugs, and has many functions such as synthesizing and decomposing proteins, regulating systemic blood volume, excluding body toxins, and regulating immunity [1]
The chemical compounds NZ, meisoindigo, and others can inhibit M1 macrophage polarization, which is associated with the downregulation of the TLR4/nuclear factor-kB (NF-kB) signaling pathway [38, 40]. These findings sufficiently indicate the critical role of TLR4/NF-kB signaling pathway in M1 macrophage polarization
These results suggest that M2 macrophage polarization inhibition and M1related inflammatory factor secretion may contribute to the inhibition of virus replication and infection, alleviating viral hepatitis and inhibiting related fibrosis
Summary
The liver is an essential organ for maintaining normal life activities of the human body, because it regulates the metabolism of many nutrients and chemical drugs, and has many functions such as synthesizing and decomposing proteins, regulating systemic blood volume, excluding body toxins, and regulating immunity [1]. A large body of literature has shown that macrophage polarization plays a crucial role in many pathophysiological processes, such as inflammation, tumor, tissue repair, and metabolism [11,12,13]. These pathological processes are precisely present in liver diseases, suggesting that macrophage polarization may be critically involved in the development and reversal of several liver diseases, such as fatty liver disease, hepatitis, fibrosis, and HCC [14,15,16]. It is hoped to provide direction and basis for future research on the mechanism of macrophage polarization and on the treatment of liver diseases via regulating macrophage polarization
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