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Updated: May 22, 2026
09:12
A Mouse Model of Chronic Liver Fibrosis for the Study of Biliary Atresia
Published on: February 3, 2023
Myeloid ATF3 Protects Against Liver Fibrosis by Modulating the Extracellular Microenvironment and Macrophage
Hao Ling1, Yanzhu Hu1, Janset Onyuru1
1Department of Surgery, Klinikum Rechts der Isar, TUM School of Medicine and Health, Technical University of Munich, Munich, Germany.
Summary
Myeloid cell-specific Activating Transcription Factor 3 (ATF3) protects against liver fibrosis by reducing inflammation and matrix deposition. Loss of ATF3 in myeloid cells worsens liver injury and fibrosis progression.
Area of Science:
- Immunology
- Hepatology
- Molecular Biology
Background:
- Activating transcription factor 3 (ATF3) is a stress-inducible factor involved in inflammation.
- Its specific role in liver fibrosis, particularly in myeloid cells, is not fully understood.
Purpose of the Study:
- To investigate the function of myeloid cell-specific ATF3 in carbon tetrachloride (CCl4)-induced liver fibrosis.
- To elucidate the mechanisms by which ATF3 influences liver injury and fibrogenesis.
Main Methods:
- Used myeloid-specific Atf3 knockout mice and wild-type littermate controls.
- Induced liver fibrosis using carbon tetrachloride (CCl4).
- Assessed liver injury, fibrosis, hepatic stellate cell activation, macrophage populations, and molecular signaling pathways.
Main Results:
- Myeloid ATF3 deficiency significantly worsened CCl4-induced liver injury, collagen deposition, and fibrosis scores.
- ATF3 loss increased hepatic stellate cell activation and shifted macrophage populations towards pro-inflammatory subtypes.
- Mechanistically, ATF3 deficiency led to increased inflammatory chemokines, reduced matrix metalloproteinases, and enhanced TGF-β1/SMAD signaling.
Conclusions:
- Myeloid ATF3 acts as a protective factor in liver fibrosis, restraining inflammation and extracellular matrix accumulation.
- Targeting ATF3-dependent pathways could offer a therapeutic strategy for fibrotic liver diseases.
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