ArticleArthritis research & therapy2023
ACSL4 inhibition prevents macrophage ferroptosis and alleviates fibrosis in bleomycin-induced systemic sclerosis model.
Article in Arthritis research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 41 citations in OpenAlex.
- Breaking the cycle of fibrosis: Ferroptosis as a therapeutic target (Review).International journal of molecular medicine · 2026Review
- Exploring Ferroptosis: A Key Mechanism in Respiratory System Diseases and its Therapeutic Potential.Applied biochemistry and biotechnology · 2026Review
- Comparative Transcriptomics Reveals Potential Regulatory Mechanisms Underlying Changes in Antioxidant, Anti-Inflammatory, and Other Immune Functions Induced byAntioxidants (Basel, Switzerland) · 2026Article
- Monocyte-Derived Macrophage Ferroptosis Amplifies Cholangitis in Primary Biliary Cholangitis via a Calpain/ACSL4 Axis.Biomedicines · 2026Article
- Ferroptosis as a Pathogenic Mechanism and Therapeutic Target in Autoimmune and Inflammatory Skin Diseases.Clinical reviews in allergy & immunology · 2026Review
- Acyl-CoA Synthetase Long-Chain Family Member 4 in Liver Injury: Multidimensional Regulation and Therapeutic Potential.Gastroenterology research · 2026Review
- Modulation of Macrophage ferroptosis under the guide of infrared thermography promotes the healing of pressure injuries.Journal of advanced research · 2026Article
- Immunohistochemical evaluation of acyl-CoA synthetase long-chain family member 4 (ACSL4) immunoreactivity in malignant melanoma specimens.Histochemistry and cell biology · 2026Article
- Metabolic-Immune Coupling in Urologic Cancers: Macrophage Reprogramming as a Therapeutic Nexus.International journal of biological sciences · 2026Review
- Exploring the common ferroptosis-related genes and molecular mechanisms in periodontitis and systemic sclerosis via integrated bioinformatics and experimental analysis.Frontiers in cell and developmental biology · 2026Article
- Targeting AASS alleviates neurotoxicity and improves mitochondrial function in astrocyte models for pyridoxine-dependent epilepsy.Molecular therapy. Nucleic acids · 2025Article
- ALK5 inhibitor impact on bleomycin-induced systemic sclerosis mouse model via multifunctional optical coherence tomography.APL bioengineering · 2025Article
- Immune cells dying from ferroptosis: mechanisms and therapeutic opportunities.Cell death & disease · 2025Review
- Long-chain acyl-CoA synthetases: biological functions, diseases and therapeutic targets.Molecular biomedicine · 2025Review
- Iron metabolism dysregulation and ferroptosis: Emerging drivers in pulmonary fibrosis pathogenesis and therapy.Molecules and cells · 2025Review
- [Research progress on cellular metabolic reprogramming in skin fibrosis].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2025Review
- ACSL4 Drives C5a/C5aR1-Calcium-Induced Fibroblast-to-Myofibroblast Transition in a Bleomycin-Induced Mouse Model of Pulmonary Fibrosis.Biomolecules · 2025Article
- Iron-Immune Crosstalk at the Maternal-Fetal Interface: Emerging Mechanisms in the Pathogenesis of Preeclampsia.Antioxidants (Basel, Switzerland) · 2025Review
- IFN-γ could induce ferroptosis in keloid fibroblasts by inhibiting the expression of serpine2.Cell death discovery · 2025Article
- Ferroptosis: the potential key roles in idiopathic pulmonary fibrosis.European journal of medical research · 2025Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSystemic sclerosis (SSc), with unclear pathophysiology, is a paradigmatic rheumatic disease of immunity dysfunction-driven multi-organ inflammation and ultimate fibrosis. Pathogenesis breakthroughs are urgently needed for available treatments halting its unremitting stiffness. This study aims to investigate whether ferroptosis can regulate the progressive SSc fibrosis.
methodsIn vivo, bleomycin (BLM)-induced mice model was subjected to ferroptosis detection using western blotting, malondialdehyde (MDA), and glutathione (GSH) assays. Pharmacological inhibitor of the acyl-CoA synthetase long-chain family member 4 (ACSL4) was utilized to explore its potential therapeutic effects for fibrosis, from histological, biochemical, and molecular analyses. In vitro, bone marrow-derived macrophages (BMDM) were activated into inflammatory phenotype and then the relationship was evaluated between activation level and ferroptosis sensitivity in lipopolysaccharide (LPS) incubation with gradient concentrations. The potential calpain/ACSL4 axis was analyzed after calpain knockdown or over-expression in Raw264.7.
resultsBoth skin and lung tissue ferroptosis were present in SSc mice with enhanced ACSL4 expression, while ACSL4 inhibition effectively halted fibrosis progressing and provides protection from inflammatory milieu. Meanwhile, a positive regulation relationship between LPS-induced macrophage activity and ferroptosis sensitivity can be observed. After calpain knockdown, both inflammatory macrophage ferroptosis sensitivity and ACSL4 expression decreased, while its over-expression renders ACSL4-envoking condition. Also, calpain pharmacological inhibition reduced both ferroptosis and fibrosis aptitude in mice.
conclusionsACSL4 induces inflammatory macrophage ferroptosis to aggravate fibrosis progressing. ACSL4 and its upregulators of calpains may be potential therapeutic targets for BLM model of SSc.
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