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<p>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.</p>

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The heterogeneity of monocyte-derived macrophages in MASH pathogenesis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月1日

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  • Miao Zhang,
  • Erzhuo Xia,
  • Chongxiao Li,
  • Shuoyi Ma,
  • Fangfang Yang,
  • Siyuan Tian,
  • Xia Zhou,
  • Xiaohong Zheng,
  • Bo Li,
  • Hui Yang,
  • Jingbo Wang,
  • Ying Han

摘要

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.