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Isolation Protocol of Mouse Monocyte-derived Dendritic Cells and Their Subsequent In Vitro Activation with Tumor Immune Complexes
Published on: May 31, 2018
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F13A1-Mediated Macrophage Activation Promotes MASH Progression via the PKM2/HIF1A Pathway.
Qianrang Lu1,2, Meiching Ong1,2, Xuewen Yi1,2
1Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|December 19, 2025
Summary
Coagulation Factor XIII-A (F13A1)-positive macrophages drive inflammation in metabolic-associated steatohepatitis (MASH). Targeting the F13A1/PKM2/HIF1A pathway offers a novel therapeutic strategy for MASH.
Area of Science:
- Hepatology
- Immunology
- Molecular Biology
Background:
- Macrophages are key players in liver inflammation and fibrosis in MASH.
- Mechanisms of macrophage activation in MASH are not fully understood.
Purpose of the Study:
- Identify the predominant macrophage subset in MASH livers.
- Elucidate the molecular mechanisms driving MASH-associated macrophage activation.
- Investigate F13A1 as a potential therapeutic target.
Main Methods:
- Single-nucleus transcriptomic analysis of human MASH livers.
- Validation in patient samples and murine models.
- In vivo gene silencing and pharmacologic interventions.
- Biochemical assays to study protein interactions and metabolic reprogramming.
Main Results:
- F13A1-positive macrophages are the predominant subset in MASH livers.
- Lipid-stressed hepatocytes induce F13A1 via S1P signaling.
- F13A1 silencing reduces inflammation and liver injury.
- F13A1 interacts with PKM2, promoting dimerization and IL1B upregulation via the PKM2/HIF1A axis.
- F13A1 enhances the Warburg effect in macrophages.
- PKM2 activation with DASA-58 inhibits F13A1-driven inflammation.
Conclusions:
- F13A1 is a critical driver of macrophage-mediated inflammation in MASH.
- The F13A1/PKM2/HIF1A pathway is a promising therapeutic target for MASH.
- Pharmacologic targeting of PKM2 demonstrates therapeutic potential.
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