ArticleCellular and molecular life sciences : CMLS2022
Macrophages evoke autophagy of hepatic stellate cells to promote liver fibrosis in NAFLD mice via the PGE2/EP4 pathway.
Article in Cellular and molecular life sciences : CMLS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 87 citations in OpenAlex.
- Potential Targets in Nonalcoholic Steatohepatitis Based on Bioinformatics Analysis and Machine Learning Strategies.Biochemical genetics · 2026Article
- Autophagy and metabolic homeostasis: Exploration in obesity‑related metabolic diseases (Review).International journal of molecular medicine · 2026Review
- Hic-5 promotes the progression of nonalcoholic steatohepatitis by regulating hepatocellular fatty acid metabolism through the PTEN/PGE2/EP4 axis.Molecular biomedicine · 2026Article
- Integrating multi-omics and machine learning systematically deciphers cellular heterogeneity and fibrotic regulatory networks in the progression from MASLD to MASH.NPJ digital medicine · 2026Article
- Single-cell insights into hepatic fibroblasts and stellate cells: heterogeneity in matrix remodelling in development, health, and disease.Npj gut and liver · 2026Review
- Modulation of Gut Microbes and Hepatic Metabolites by PCP Ameliorates NASH and Fatigue-like Performance in Mice.Nutrients · 2025Article
- Cell-specific roles of autophagy in liver fibrosis: implications for targeted pharmacotherapy.Annals of medicine · 2025Review
- The Role of Hepatic SIRT1: From Metabolic Regulation to Immune Modulation and Multi-target Therapeutic Strategies.Journal of clinical and translational hepatology · 2025Review
- Rebamipide Induces Hair Regeneration Through EP4-Driven Lipid Metabolism Remodeling.International journal of molecular sciences · 2025Article
- Regulation of Hepatic Stellate Cell Phenotypes in Metabolic Dysfunction-Associated Steatohepatitis.Gastroenterology · 2025Review
- YKL-40 in Virus-Associated Liver Disease: A Translational Biomarker Linking Fibrosis, Hepatocarcinogenesis, and Liver Transplantation.International journal of molecular sciences · 2025Review
- [Protective effect of knock-down the expression ofBeijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2025Article
- Nogo-B Silencing Expedites the Senescence of Platelet-Derived Growth Factor-BB-Induced Human Hepatic Stellate Cells Via Autophagy.Molecular biotechnology · 2025Article
- Identification of prognostic and therapeutic biomarkers associated with macrophage and lipid metabolism in pancreatic cancer.Scientific reports · 2025Article
- Macrophage miR-4524a-5p/TBP promotes β-TrCP -TIM3 complex activation and TGFβ release and aggravates NAFLD-associated fibrosis.Cell death & disease · 2025Article
- Single-Cell Sequencing Reveals the Heterogeneity of Hepatic Natural Killer Cells and Identifies the Cytotoxic Natural Killer Subset in Schistosomiasis Mice.International journal of molecular sciences · 2025Article
- Targeting the E Prostanoid Receptor EP4 Mitigates Cardiac Fibrosis Induced by β-Adrenergic Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting fatty acid synthase reduces aortic atherosclerosis and inflammation.Communications biology · 2025Article
- Identification of regulatory cell death-related genes during MASH progression using bioinformatics analysis and machine learning strategies.Frontiers in immunology · 2025Article
- Three-Dimensional Dynamic Cell Models for Metabolic Dysfunction-Associated Steatotic Liver Disease Progression.BME frontiers · 2025Article
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Authors and funding
16 authors at 1 institution in 2 countries.
Funding
Abstract
The pathogenesis of liver fibrosis in nonalcoholic fatty liver disease (NAFLD) remains unclear and the effective treatments have not been explored yet. The activation of hepatic stellate cells (HSCs) is considered as the most critical factor in the progression of liver fibrosis and cirrhosis. Autophagy has recently been identified as a new mechanism to regulate HSC activation. Here, we found that liver macrophages were polarized toward type 2 (M2) during the progression of nonalcoholic steatohepatitis (NASH) and liver fibrosis in both patients and NAFLD mice. Using the methionine-choline-deficient (MCD) diet NAFLD murine model and the in vitro cell culture system, we identified that the M2 macrophages promoted HSC autophagy by secreting prostaglandin E2 (PGE2) and binding its receptor EP4 on the surface of HSCs, which consequently enhanced HSC activation, extracellular matrix deposition, and liver fibrosis. Mechanistically, PGE2/EP4 signals enhanced HSC autophagy through the Erk pathway. A specific PGE2/EP4 antagonist E7046 significantly inhibited M2 macrophage-mediated HSC autophagy and improved liver fibrosis and histopathology in NAFLD mice. Our study provides novel mechanistic insights into the regulation of HSC activation and liver fibrosis. Our findings suggest that the PGE2/EP4 pathway is a promising therapeutic target to prevent NASH progression into cirrhosis.
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