ArticleJournal of cellular and molecular medicine2021
Pirfenidone modulates macrophage polarization and ameliorates radiation-induced lung fibrosis by inhibiting the TGF-β1/Smad3 pathway.
Article in Journal of cellular and molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.
- The Role of Monocytes in the Natural History of Idiopathic Pulmonary Fibrosis: A Systematic Literature Review.International journal of molecular sciences · 2025Pooled it
- Macrophage polarization plasticity in pulmonary fibrosis: a review from pathogenesis to therapeutic targeting.Inflammopharmacology · 2026Review
- Macrophage heterogeneity in organ fibrosis in the era of single-cell omics.Molecular biology reports · 2026Review
- Targeting alveolar type II cell dysfunction in idiopathic pulmonary fibrosis: Molecular mechanisms and emerging therapeutic strategies (Review).International journal of molecular medicine · 2026Review
- BCL9 inhibition promotes fibroblast lipogenesis by regulating macrophage-fibroblast interactions to attenuate pulmonary fibrosis.Signal transduction and targeted therapy · 2026Article
- Advances in pharmacotherapy for fibrotic interstitial lung disease.Medical review (2021) · 2026Review
- Identification of TGF-β1 as a key regulator in DOX-induced cardiotoxicity.Journal of cardiothoracic surgery · 2026Article
- Research trends and hot topics of radiation-induced pulmonary fibrosis: a bibliometric analysis and visualization study from 2015 to 2025.Journal of thoracic disease · 2026Article
- Cilostazol mitigates amiodarone-induced pulmonary toxicity and fibrosis by regulating the cAMP/TGF-β1 pathway-mediated epithelial-to-mesenchymal transition in rats.Scientific reports · 2026Article
- Oxidized mtDNA Contributes to Pulmonary Inflammation and Fibrosis in Bleomycin-Induced Lung Injury.MedComm · 2026Article
- "One stone three birds": Andrographis paniculata -derived exosome-like nanoparticles mitigate dextran sulfate sodium-induced colitis.Chinese medical journal · 2026Article
- Radiomitigators: Breakthroughs in Post-Radiation Recovery.Antioxidants (Basel, Switzerland) · 2026Review
- Furazolidone-associated drug-induced interstitial lung disease: A case report and literature review.The Journal of international medical research · 2026Review
- SFRP4 Knockdown Attenuates Dsg2-Deficient Arrhythmogenic Cardiomyopathy by Down-Regulating TGF-β and Smad3.Biochemical genetics · 2026Article
- Mechanistic Evaluation of Roxadustat for Pulmonary Fibrosis: Integrating Network Pharmacology, Transcriptomics, and Experimental Validation.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Ionizing radiation: molecular mechanisms, biological effects, and therapeutic targets.Molecular biomedicine · 2026Review
- Rubiadin-1-methyl ether alleviates bleomycin induced pulmonary fibrosis.Scientific reports · 2026Article
- Article
- Molecular mechanisms and network interactions in radiation-induced lung injury.Frontiers in physiology · 2026Review
- Beyond attenuation: a translational review of curative-intent pharmacological targets in idiopathic pulmonary fibrosis.Frontiers in medicine · 2026Review
16 more citing papers are in PubMed but not listed here.
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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
Radiation-induced lung injury (RILI) mainly contributes to the complications of thoracic radiotherapy. RILI can be divided into radiation pneumonia (RP) and radiation-induced lung fibrosis (RILF). Once RILF occurs, patients will eventually develop irreversible respiratory failure; thus, a new treatment strategy to prevent RILI is urgently needed. This study explored the therapeutic effect of pirfenidone (PFD), a Food and Drug Administration (FDA)-approved drug for (IPF) treatment, and its mechanism in the treatment of RILF. In vivo, C57BL/6 mice received a 50 Gy dose of X-ray radiation to the whole thorax with or without the administration of PFD. Collagen deposition and fibrosis in the lung were reversed by PFD treatment, which was associated with reduced M2 macrophage infiltration and inhibition of the transforming growth factor-β1 (TGF-β1)/Drosophila mothers against the decapentaplegic 3 (Smad3) signalling pathway. Moreover, PFD treatment decreased the radiation-induced expression of TGF-β1 and phosphorylation of Smad3 in alveolar epithelial cells (AECs) and vascular endothelial cells (VECs). Furthermore, IL-4-induced M2 macrophage polarization and IL-13-induced M2 macrophage polarization were suppressed by PFD treatment in vitro, resulting in reductions in the release of arginase-1 (ARG-1), chitinase 3-like 3 (YM-1) and TGF-β1. Notably, the PFD-induced inhibitory effects on M2 macrophage polarization were associated with downregulation of nuclear factor kappa-B (NF-κB) p50 activity. Additionally, PFD could significantly inhibit ionizing radiation-induced chemokine secretion in MLE-12 cells and consequently impair the migration of RAW264.7 cells. PFD could also eliminate TGF-β1 from M2 macrophages by attenuating the activation of TGF-β1/Smad3. In conclusion, PFD is a potential therapeutic agent to ameliorate fibrosis in RILF by reducing M2 macrophage infiltration and inhibiting the activation of TGF-β1/Smad3.
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