ArticleJCI insight2020
Epigenetic regulation of the PGE2 pathway modulates macrophage phenotype in normal and pathologic wound repair.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 76 citations in OpenAlex.
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- Dietary omega-6 lipids promote postinjury aberrant bone formation in obesity.The Journal of clinical investigation · 2026Article
- Adhesive Hydrogel Loaded with Sulfonated Chitosan Promotes Oral Mucosal Defect Repair in Diabetic Rats.Bioengineering (Basel, Switzerland) · 2026Article
- Therapeutic implications of epigenetic alterations in burns: a new frontier in burn medicine.Clinical science (London, England : 1979) · 2026Review
- Carbomol hydrogels integrating chlorogenic acid-loaded exosomes promote diabetic wound healing through antibacterial and immunomodulatory activities.Biology direct · 2026Article
- Nuclear deformation acts as a mechanical switch to drive breast cancer cell migration in a confined microenvironment.Theranostics · 2026Article
- Histone post-translational modifications in diabetic foot ulcer healing: linking immune dysregulation to tissue repair.Frontiers in immunology · 2026Review
- Single-cell RNA sequencing in diabetic foot ulcers: pathogenesis, biomarkers, and translational potential.Frontiers in clinical diabetes and healthcare · 2026Review
- The role of macrophage polarization in organ transplantation: research progress on impact on graft injury, repair, and fibrosis.Frontiers in immunology · 2026Review
- IL-17A is increased in diabetic wounds and impairs keratinocyte function via histone demethylase JMJD3.Nature communications · 2025Article
- TNF-α represses fibroblast to myofibroblast transition through the histone methyltransferase Setdb2.JCI insight · 2025Article
- Discovery and Mechanistic Elucidation of Glycyrrhizic Acid Composite Gel in Promoting Wound Healing: A Modernized Study Based on Shengji Yuhong Ointment.Pharmaceuticals (Basel, Switzerland) · 2025Article
- EGFR-STAT1 pathway drives fibrosis initiation in fibroinflammatory skin diseases.Nature communications · 2025Article
- Application of Biomaterials in Diabetic Wound Healing: The Recent Advances and Pathological Aspects.Pharmaceutics · 2025Review
- Macrophage HM13/SPP Enhances Foamy Macrophage Formation and Atherogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Nanoparticle-Reinforced Hydrogel with a Well-Defined Pore Structure for Sustainable Drug Release and Effective Wound Healing.ACS applied bio materials · 2025Article
- LPCAT3 regulates the proliferation and metastasis of serous ovarian cancer by modulating arachidonic acid.Translational oncology · 2025Article
- Article
- Prostaglandin EEXCLI journal · 2025Review
- Epigenetic regulatory mechanism of macrophage polarization in diabetic wound healing (Review).Molecular medicine reports · 2025Review
Corrections and comments
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Authors and funding
21 authors at 4 institutions in 2 countries.
Funding
Abstract
Macrophages are a primary immune cell involved in inflammation, and their cell plasticity allows for transition from an inflammatory to a reparative phenotype and is critical for normal tissue repair following injury. Evidence suggests that epigenetic alterations play a critical role in establishing macrophage phenotype and function during normal and pathologic wound repair. Here, we find in human and murine wound macrophages that cyclooxygenase 2/prostaglandin E2 (COX-2/PGE2) is elevated in diabetes and regulates downstream macrophage-mediated inflammation and host defense. Using single-cell RNA sequencing of human wound tissue, we identify increased NF-κB-mediated inflammation in diabetic wounds and show increased COX-2/PGE2 in diabetic macrophages. Further, we identify that COX-2/PGE2 production in wound macrophages requires epigenetic regulation of 2 key enzymes in the cytosolic phospholipase A2/COX-2/PGE2 (cPLA2/COX-2/PGE2) pathway. We demonstrate that TGF-β-induced miRNA29b increases COX-2/PGE2 production via inhibition of DNA methyltransferase 3b-mediated hypermethylation of the Cox-2 promoter. Further, we find mixed-lineage leukemia 1 (MLL1) upregulates cPLA2 expression and drives COX-2/PGE2. Inhibition of the COX-2/PGE2 pathway genetically (Cox2fl/fl Lyz2Cre+) or with a macrophage-specific nanotherapy targeting COX-2 in tissue macrophages reverses the inflammatory macrophage phenotype and improves diabetic tissue repair. Our results indicate the epigenetically regulated PGE2 pathway controls wound macrophage function, and cell-targeted manipulation of this pathway is feasible to improve diabetic wound repair.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.