The heterogeneity of monocyte-derived macrophages in MASH pathogenesis
Miao Zhang1, Erzhuo Xia1, Chongxiao Li1
1Xijing Hospital of Digestive Diseases, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Air Force Medical University, Xi'an, China.
Abstract:
Metabolic dysfunction-associated fatty liver disease (MAFLD) is the leading global cause of chronic liver disease. Its more severe inflammatory form, metabolic dysfunction-associated steatohepatitis (MASH), often progresses to cirrhosis and hepatocellular carcinoma. However, the pathogenic mechanisms underlying MASH remain insufficiently defined. Hepatic macrophages, particularly monocyte-derived macrophages (MDMs), have recently been identified as key mediators in disease progression. This review summarizes the current evidence on the heterogeneity of MDMs in MASH pathogenesis, focusing on distinct subsets and their roles in either promoting or resolving hepatic inflammation. Additionally, the review provides an in-depth exploration of the mechanisms driving MDM differentiation, which contribute to their functional diversity. A more comprehensive understanding of MASH pathogenesis is essential for the identification of novel and effective therapeutic targets.
Insights
Metabolic dysfunction-associated steatohepatitis (MASH) involves hepatic macrophages. Understanding monocyte-derived macrophage (MDM) diversity is key to finding new treatments for this severe liver disease.
Area of Science:
- Hepatology
- Immunology
- Cell Biology
Background:
- Metabolic dysfunction-associated fatty liver disease (MAFLD) is a leading cause of chronic liver disease globally.
- Its inflammatory form, metabolic dysfunction-associated steatohepatitis (MASH), can lead to cirrhosis and cancer.
- The precise mechanisms driving MASH progression are not fully understood.
Purpose of the Study:
- To review the heterogeneity of hepatic monocyte-derived macrophages (MDMs) in MASH pathogenesis.
- To explore the roles of distinct MDM subsets in hepatic inflammation.
- To examine the mechanisms governing MDM differentiation and functional diversity.
Main Methods:
- Literature review of current evidence on MDMs in MASH.
- Analysis of MDM heterogeneity and functional roles.
- Exploration of MDM differentiation pathways.
Main Results:
- Hepatic MDMs are identified as key mediators in MASH progression.
- Distinct MDM subsets exhibit diverse functions, influencing hepatic inflammation.
- Understanding MDM differentiation mechanisms is crucial for their functional diversity.
Conclusions:
- Hepatic MDMs play a critical role in MASH pathogenesis.
- Targeting specific MDM subsets or their differentiation pathways may offer therapeutic strategies.
- Further research into MDM heterogeneity is essential for developing effective MASH treatments.
