ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
Tetrahedral DNA loaded siCCR2 restrains M1 macrophage polarization to ameliorate pulmonary fibrosis in chemoradiation-induced murine model.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 18 citations in OpenAlex.
- Phloridzin mitigates bleomycin-elicited lung fibrosis in Wistar rats: The interplay between antioxidant defenses, inflammatory processes, transforming growth factor beta 1, and autophagy.Toxicology reports · 2026Article
- Exploring the role of RCEO in macrophage-mediated modulation of pulmonary fibrosis.Chinese medicine · 2026Article
- Hdac11 promotes idiopathic pulmonary fibrosis through macrophage M2-type polarization and myofibroblast accumulation by inhibiting Parkin-dependent mitophagy.Nature communications · 2026Article
- Tetrahedral framework nucleic acid delivery of emodin enables precision antibacterial and anti-inflammatory therapy for drug-resistant Staphylococcus aureus.Journal of nanobiotechnology · 2026Article
- Advances in Tetrahedral Framework Nucleic Acids (tFNAs) for Lung Injury Repair: Mechanisms, Therapeutic Applications, and Future Directions.International journal of nanomedicine · 2026Review
- Recruited Monocyte-Derived Macrophages Drive T Cell Inflammation in Immune Checkpoint Inhibitor-Mediated Pneumonitis.Cancer communications (London, England) · 2026Article
- From inflammatory activation to fibrotic remodeling: the central role of macrophage heterogeneity in frozen shoulder.Frontiers in immunology · 2026Review
- The gene regulatory networks shaping macrophage plasticity and altered function in fibrosis.Frontiers in immunology · 2026Review
- Epigenetic regulatory mechanisms and translational applications in idiopathic pulmonary fibrosis.American journal of clinical and experimental immunology · 2026Review
- Unraveling the pleiotropic effects of CCR2-dependent signal transduction in fibrosis development.Theranostics · 2026Review
- The rise and fall of glucocorticoids and immunosuppressants in idiopathic pulmonary fibrosis: a historical paradigm shift driven by mechanistic understanding.Frontiers in immunology · 2026Review
- Idiopathic Pulmonary Fibrosis: Cellular Heterogeneity, Mechanisms, and Therapeutic Implications.MedComm · 2025Review
- The spatial and temporal activation of macrophages during fibrosis.Nature reviews. Immunology · 2025Review
- Inhalable myofibroblast targeting nanoparticles for synergistic treatment of pulmonary fibrosis.Science advances · 2025Article
- Current Understanding and Translational Prospects of Tetrahedral Framework Nucleic Acids.JACS Au · 2025Review
- The role of natural products targeting macrophage polarization in sepsis-induced lung injury.Chinese medicine · 2025Review
- Common biomarkers of idiopathic pulmonary fibrosis and systemic sclerosis based on WGCNA and machine learning.Scientific reports · 2025Article
- Iguratimod improves bleomycin-induced pulmonary inflammation and fibrosis by regulating macrophage polarization through inhibiting the TLR4/NF-κB pathway.Frontiers in immunology · 2025Article
- The role and therapeutic targeting of the CCL2/CCR2 signaling axis in inflammatory and fibrotic diseases.Frontiers in immunology · 2024Review
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Authors and funding
19 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic lethal disease in the absence of demonstrated efficacy for preventing progression. Although macrophage-mediated alveolitis is determined to participate in myofibrotic transition during disease development, the paradigm of continuous macrophage polarization is still under-explored due to lack of proper animal models. Here, by integrating 2.5 U/kg intratracheal Bleomycin administration and 10 Gy thorax irradiation at day 7, we generated a murine model with continuous alveolitis-mediated fibrosis, which mimics most of the clinical features of our involved IPF patients. In combination with data from scRNA-seq of patients and a murine IPF model, a decisive role of CCL2/CCR2 axis in driving M1 macrophage polarization was revealed, and M1 macrophage was further confirmed to boost alveolitis in leading myofibroblast activation. Multiple sticky-end tetrahedral framework nucleic acids conjunct with quadruple ccr2-siRNA (FNA-siCCR2) was synthesized in targeting M1 macrophages. FNA-siCCR2 successfully blocked macrophage accumulation in pulmonary parenchyma of the IPF murine model, thus preventing myofibroblast activation and leading to the disease remitting. Overall, our studies lay the groundwork to develop a novel IPF murine model, reveal M1 macrophages as potential therapeutic targets, and establish new treatment strategy by using FNA-siCCR2, which are highly relevant to clinical scenarios and translational research in the field of IPF.
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