ArticleRespiratory research2021
Inhibition of EZH2 prevents acute respiratory distress syndrome (ARDS)-associated pulmonary fibrosis by regulating the macrophage polarization phenotype.
Article in Respiratory research, 2021. 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, 72 citations in OpenAlex.
- Review
- Autophagy-epithelial-mesenchymal transition crosstalk in acute respiratory distress syndrome: Mechanistic insights and therapeutic perspectives (Review).Experimental and therapeutic medicine · 2026Review
- The regulation of oxidative stress response by epigenetic modifications in acute respiratory distress syndrome.Journal of thoracic disease · 2026Review
- Article
- The Role of Histone Modifications in Acute Lung Injury: Molecular Mechanisms and Potential of Traditional Chinese Medicine Treatment.Journal of inflammation research · 2026Review
- Succinic Acid-Induced Macrophage Endocytosis Promotes Extracellular Vesicle-Based Integrin Beta1 Transfer Accelerating Fibroblast Activation and Sepsis-Associated Pulmonary Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Epigenetic reprogramming via EZH2 inhibition rescues fibroadipose pathogenesis in secondary lymphedema through activating PPARγ signaling.Journal of orthopaedic translation · 2025Article
- The Immune Microenvironment: New Therapeutic Implications in Organ Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Toll-Interacting Protein Down-Regulation by Cigarette Smoke Exposure Impairs Human Lung Defense against Influenza A Virus Infection.The American journal of pathology · 2025Article
- Let-7 restrains an epigenetic circuit in AT2 cells to prevent fibrogenic intermediates in pulmonary fibrosis.Nature communications · 2025Article
- Pulmonary fibrosis: from mechanisms to therapies.Journal of translational medicine · 2025Review
- Decoding immune-metabolic crosstalk in ARDS: a transcriptomic exploration of biomarkers, cellular dynamics, and therapeutic pathways.Frontiers in immunology · 2025Article
- Macrophages and Pulmonary Fibrosis.Current molecular medicine · 2025Review
- Lysine methylation modifications in tumor immunomodulation and immunotherapy: regulatory mechanisms and perspectives.Biomarker research · 2024Review
- Effect of apigetrin in pseudo-SARS-CoV-2-induced inflammatory and pulmonary fibrosis in vitro model.Scientific reports · 2024Article
- PROTAC EZH2 degrader-1 overcomes the resistance of podophyllotoxin derivatives in refractory small cell lung cancer with leptomeningeal metastasis.BMC cancer · 2024Article
- EZH2 as a major histone methyltransferase in PDGF-BB-activated orbital fibroblast in the pathogenesis of Graves' ophthalmopathy.Scientific reports · 2024Article
- H3K27Me3 abundance increases fibrogenesis during endothelial-to-mesenchymal transition via the silencing of microRNA-29c.Frontiers in cardiovascular medicine · 2024Article
- Non-canonical function of histone methyltransferase G9a in the translational regulation of chronic inflammation.Cell chemical biology · 2023Article
- Grape Seed Proanthocyanidin Ameliorates LPS-induced Acute Lung Injury By Modulating M2a Macrophage Polarization Via the TREM2/PI3K/Akt Pathway.Inflammation · 2023Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundWe recently reported histone methyltransferase enhancer of zeste homolog 2 (EZH2) as a key epigenetic regulator that contributes to the dysfunction of innate immune responses to sepsis and subsequent lung injury by mediating the imbalance of macrophage polarization. However, the role of EZH2 in acute respiratory distress syndrome (ARDS)-associated fibrosis remains poorly understood.
methodsIn this study, we investigated the role and mechanisms of EZH2 in pulmonary fibrosis in a murine model of LPS-induced ARDS and in ex-vivo cultured alveolar macrophages (MH-S) and mouse lung epithelial cell line (MLE-12) by using 3-deazaneplanocin A (3-DZNeP) and EZH2 the small interfering (si) RNA.
resultsWe found that treatment with 3-DZNeP significantly ameliorated the LPS-induced direct lung injury and fibroproliferation by blocking EMT through TGF-β1/Smad signaling pathway and regulating shift of macrophage phenotypes. In the ex-vivo polarized alveolar macrophages cells, treatment with EZH2 siRNA or 3-DZNeP suppressed the M1 while promoted the M2 macrophage differentiation through modulating the STAT/SOCS signaling pathway and activating PPAR-γ. Moreover, we identified that blockade of EZH2 with 3-DZNeP suppressed the epithelial to mesenchymal transition (EMT) in co-cultured bronchoalveolar lavage fluid (BALF) and mouse lung epithelial cell line through down-regulation of TGF-β1, TGF-βR1, Smad2 while up-regulation of Smad7 expression.
conclusionsThese results indicate that EZH2 is involved in the pathological process of ARDS-associated pulmonary fibrosis. Targeting EZH2 may be a potential therapeutic strategy to prevent and treat pulmonary fibrosis post ARDS.
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