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Role of Macrophages in Liver Fibrosis
Cuiming Sun1,2, Akihiro Matsukawa1
1Department of Pathology and Experimental Medicine, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences.
Abstract:
Liver fibrosis, which ultimately leads to liver cirrhosis and hepatocellular carcinoma, is a major health burden worldwide. The progression of liver fibrosis is the result of the wound-healing response of liver to repeated injury. Hepatic macrophages are cells with high heterogeneity and plasticity and include tissue-resident macrophages termed Kupffer cells, and recruited macrophages derived from circulating monocytes, spleen and peritoneal cavity. Studies have shown that hepatic macrophages play roles in the initiation and progression of liver fibrosis by releasing inflammatory cytokines/chemokines and pro-fibrogenic factors. Furthermore, the development of liver fibrosis has been shown to be reversible. Hepatic macrophages have been shown to alternately regulate both the regression and turnover of liver fibrosis by changing their phenotypes during the dynamic progression of liver fibrosis. In this review, we summarize the role of hepatic macrophages in the progression and regression of liver fibrosis.
Insights
Hepatic macrophages drive liver fibrosis progression and regression. These versatile cells, including Kupffer cells and monocyte-derived macrophages, can be targeted to potentially reverse liver damage and disease.
Area of Science:
- Hepatology and Immunology
- Cellular Biology and Disease Mechanisms
Background:
- Liver fibrosis, a precursor to cirrhosis and liver cancer, represents a significant global health issue.
- Fibrosis arises from the liver's wound-healing response to persistent injury.
- Hepatic macrophages, comprising Kupffer cells and monocyte-derived cells, are key players in liver inflammation and injury.
Purpose of the Study:
- To review the multifaceted roles of hepatic macrophages in both the advancement and resolution of liver fibrosis.
- To highlight the dynamic phenotypes of hepatic macrophages and their impact on fibrosis progression and regression.
Main Methods:
- Literature review synthesizing current research on hepatic macrophage biology and liver fibrosis.
- Analysis of studies investigating macrophage phenotypes and their functional consequences in liver fibrogenesis and resolution.
Main Results:
- Hepatic macrophages contribute to liver fibrosis initiation and progression through inflammatory and pro-fibrogenic factor release.
- The plasticity of hepatic macrophages allows them to modulate fibrosis, promoting both its advancement and regression.
- Phenotypic changes in hepatic macrophages are critical for regulating the dynamic turnover of liver fibrotic tissue.
Conclusions:
- Hepatic macrophages are central regulators of liver fibrosis, influencing its progression and reversibility.
- Targeting hepatic macrophage phenotypes offers a potential therapeutic strategy for managing and reversing liver fibrosis.
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