ArticleThe Journal of clinical investigation2022
Genome-wide DNA hypermethylation opposes healing in patients with chronic wounds by impairing epithelial-mesenchymal transition.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 49 citations in OpenAlex.
- Reimagining VEGF Therapy: The Role of PLCγ2 in Pan-Organ Endothelial Networks.Advances in wound care · 2026Article
- Microbiome-guided cancer immunotherapy: immune mechanisms, resistance pathways, and translational opportunities for precision oncology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Trimodal, uncertainty-guided whole-slide framework for genome-scale spatial expression and image-only virtual perturbation in cancer cohorts.Genome medicine · 2026Article
- Diabetic Wound Vasculopathy and Neuropathy: Spotlight on Wound Lipid Signaling.Advances in wound care · 2026Review
- Agonal cell resuscitation strategy to promote tissue repair.Nature communications · 2026Article
- Elucidating the mechanisms by which acetyl tributyl citrate affects fracture healing: a comprehensive network toxicology study.BMC pharmacology & toxicology · 2026Article
- Applications of Nanomaterials in Chronic Wound Healing and Scar Prevention.International journal of nanomedicine · 2026Review
- Long-term cytokine exposure remodels the methylome and transcriptome of recessive dystrophic epidermolysis bullosa keratinocytes - a bioinformatic analysis.Frontiers in cell and developmental biology · 2026Article
- A transcriptome-wise Atlas of human prostate as a function of postmortem interval time.Scientific reports · 2025Article
- Direct in vivo reprogramming to relieve tissue ischemia via induced vasculogenesis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Function of epigenetic modifications in wound healing and potential therapies (Review).International journal of molecular medicine · 2025Review
- Major Common Hallmarks and Potential Epigenetic Drivers of Wound Chronicity and Recurrence: Hypothesis and Reflections.International journal of molecular sciences · 2025Review
- Cell and tissue reprogramming: Unlocking a new era in medical drug discovery.Pharmacological reviews · 2025Review
- Review
- Dual-Action flavonol carbonized polymer dots spray: Accelerating burn wound recovery through immune responses modulation and EMT induction.Materials today. Bio · 2025Article
- Nanomanaging Chronic Wounds with Targeted Exosome Therapeutics.Pharmaceutics · 2025Review
- Tissue nanotransfection-based endothelial PLCγ2-targeted epigenetic gene editing rescues perfusion and diabetic ischemic wound healing.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Tissue nanotransfection and cellular reprogramming in regenerative medicine and antimicrobial dynamics.Frontiers in bioengineering and biotechnology · 2025Review
- Bridging tissue repair and epithelial carcinogenesis: epigenetic memory and field cancerization.Cell death and differentiation · 2025Review
- Mission SpaceX CRS-16 RRRM-1 space flight induced skin genomic plasticity via an epigenetic trigger.iScience · 2024Article
Corrections and comments
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Authors and funding
28 authors at 5 institutions in 2 countries.
Funding
Abstract
An extreme chronic wound tissue microenvironment causes epigenetic gene silencing. An unbiased whole-genome methylome was studied in the wound-edge tissue of patients with chronic wounds. A total of 4,689 differentially methylated regions (DMRs) were identified in chronic wound-edge skin compared with unwounded human skin. Hypermethylation was more frequently observed (3,661 DMRs) in the chronic wound-edge tissue compared with hypomethylation (1,028 DMRs). Twenty-six hypermethylated DMRs were involved in epithelial-mesenchymal transition (EMT). Bisulfite sequencing validated hypermethylation of a predicted specific upstream regulator TP53. RNA-Seq analysis was performed to qualify findings from methylome analysis. Analysis of the downregulated genes identified the TP53 signaling pathway as being significantly silenced. Direct comparison of hypermethylation and downregulated genes identified 4 genes, ADAM17, NOTCH, TWIST1, and SMURF1, that functionally represent the EMT pathway. Single-cell RNA-Seq studies revealed that these effects on gene expression were limited to the keratinocyte cell compartment. Experimental murine studies established that tissue ischemia potently induces wound-edge gene methylation and that 5'-azacytidine, inhibitor of methylation, improved wound closure. To specifically address the significance of TP53 methylation, keratinocyte-specific editing of TP53 methylation at the wound edge was achieved by a tissue nanotransfection-based CRISPR/dCas9 approach. This work identified that reversal of methylation-dependent keratinocyte gene silencing represents a productive therapeutic strategy to improve wound closure.
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