ArticleThe Journal of clinical investigation2024
Serum amyloid A expression in liver promotes synovial macrophage activation and chronic arthritis via NFAT5.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Matrix Rigidity Mechanoprimes Microglia for Inflammation Through Cytoskeletal-to-Nuclear Signaling and 3D Spatio-Epigenomic Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting adipocyte ESRRA alleviates osteoarthritis via interrupting inter-organelle crosstalk of complement C3-CFD-MAC cascade.Bone research · 2026Article
- Fluorescence-Guided Spatial Mapping of p21-Expressing Senescent Cells in Aged Liver at Single-Cell Resolution.Biomolecules · 2026Article
- Hepatocyte TonEBP promotes metabolic stress-induced hepatic fibroinflammation involving transcriptional activation of ELR⁺ CXC chemokines.Cell death discovery · 2026Article
- Serum amyloid A: multifaceted roles in inflammation and cellular interactions.Immunologic research · 2025Review
- Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells.Cellular & molecular immunology · 2025Review
- CREB1/CRTC2 regulated tubular epithelial-derived exosomal miR-93-3p promotes kidney injury induced by calcium oxalate via activating M1 polarization and macrophage extracellular trap formation.Journal of nanobiotechnology · 2025Article
- Functional Interactions Between Recombinant Serum Amyloid A1 (SAA1) and Chemokines in Leukocyte Recruitment.International journal of molecular sciences · 2025Review
- TARGETING S100A9-TLR2 AXIS CONTROLS MACROPHAGE NLRP3 INFLAMMASOME ACTIVATION IN FATTY LIVER ISCHEMIA REPERFUSION INJURY.Shock (Augusta, Ga.) · 2025Article
- Article
- NFAT5 exacerbates β-cell ferroptosis by suppressing the transcription of PRDX2 in obese type 2 diabetes mellitus.Cellular and molecular life sciences : CMLS · 2025Article
- Recent Advances in Studies of Serum Amyloid A: Implications in Inflammation, Immunity and Tumor Metastasis.International journal of molecular sciences · 2025Review
- Balancing inflammation: the specific roles of serum amyloid A proteins in sterile and infectious diseases.Frontiers in immunology · 2025Article
- NFAT5: a stress-related transcription factor with multiple functions in health and disease.Cell stress · 2025Review
- Serum amyloid A contributes to radiation-induced lung injury by activating macrophages through FPR2/Rac1/NF-κB pathway.International journal of biological sciences · 2024Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nuclear factor of activated T-cells 5 (NFAT5), an osmo-sensitive transcription factor, can be activated by isotonic stimuli, such as infection. It remains unclear, however, whether NFAT5 is required for damage-associated molecular pattern-triggered (DAMP-triggered) inflammation and immunity. Here, we found that several DAMPs increased NFAT5 expression in macrophages. In particular, serum amyloid A (SAA), primarily generated by the liver, substantially upregulated NFAT5 expression and activity through TLR2/4-JNK signalling pathway. Moreover, the SAA-TLR2/4-NFAT5 axis promoted migration and chemotaxis of macrophages in an IL-6- and chemokine ligand 2-dependent (CCL2-dependent) manner in vitro. Intraarticular injection of SAA markedly accelerated macrophage infiltration and arthritis progression in mice. By contrast, genetic ablation of NFAT5 or TLR2/4 rescued the pathology induced by SAA, confirming the SAA-TLR2/4-NFAT5 axis in vivo. Myeloid-specific depletion of NFAT5 also attenuated SAA-accelerated arthritis. Of note, inflammatory arthritis in mice strikingly induced SAA overexpression in the liver. Conversely, forced overexpression of the SAA gene in the liver accelerated joint damage, indicating that the liver contributes to bolstering chronic inflammation at remote sites by secreting SAA. Collectively, this study underscores the importance of the SAA-TLR2/4-NFAT5 axis in innate immunity, suggesting that acute phase reactant SAA mediates mutual interactions between liver and joints and ultimately aggravates chronic arthritis by enhancing macrophage activation.
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