Myeloid ATF3 Protects Against Liver Fibrosis by Modulating the Extracellular Microenvironment and Macrophage Inflammatory Signaling - PubMed
3 hours ago
- #liver fibrosis
- #macrophage signaling
- #ATF3
- Activating transcription factor 3 (ATF3) is a stress-inducible transcription factor that regulates inflammatory responses, and its role in liver fibrosis is not fully understood.
- Myeloid-specific ATF3 knockout mice (Atf3fl/fl LysM-Cre+) were used to study liver fibrosis induced by carbon tetrachloride (CCl4).
- ATF3 deficiency worsened liver injury, shown by increased serum ALT/AST, collagen deposition, fibrosis scores, and hepatic stellate cell activation.
- While total macrophage numbers were unchanged, ATF3 loss led to more Ly6C+ infiltrating macrophages and fewer Kupffer cells.
- Mechanistically, ATF3-deficient livers had higher chemokine expression, reduced MMPs, increased TIMP1, and enhanced TGF-β1/SMAD signaling.
- Myeloid ATF3 acts as a protective factor by limiting inflammation and extracellular matrix buildup in liver fibrosis.
- Targeting ATF3 pathways could be a potential therapy for fibrotic liver disease.