ArticleWound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
Deregulation of epidermal stem cell niche contributes to pathogenesis of nonhealing venous ulcers.
Article in Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 2 syntheses or guidelines pooled it, 70 citations in OpenAlex.
- Antimicrobial photodynamic therapy in skin wound healing: A systematic review of animal studies.International wound journal · 2020Pooled it
- Transcriptomics in Venous Leg Ulcers (VLU): A Systematic Review.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair SocietyPooled it
- A bioengineered living cell construct activates an acute wound healing response in venous leg ulcers.Science translational medicine · 2017Trial
- Interplay of ELF5, GATA-3 and FLI-1 regulate malignant transformation of keratinocytes.Scientific reports · 2026Article
- The role of multi-omics in biomarker discovery, diagnosis, prognosis, and therapeutic monitoring of tissue repair and regeneration processes.Journal of orthopaedic translation · 2025Review
- Systemic immune response alteration in patients with severe pressure ulcers.Scientific reports · 2025Article
- Polyphenols in wound healing: unlocking prospects with clinical applications.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- HEALS-A and GRADES: Novel Histological and Clinical Scales for Assessing Skin Regeneration in Murine Wound Healing Models.Diagnostics (Basel, Switzerland) · 2025Article
- Recent advances in the role of neuroregulation in skin wound healing.Burns & trauma · 2025Review
- Role of Mesenchymal Stem/Stromal Cells (MSCs) and MSC-Derived Extracellular Vesicles (EVs) in Prevention of Telomere Length Shortening, Cellular Senescence, and Accelerated Biological Aging.Bioengineering (Basel, Switzerland) · 2024Review
- Molecular characterization of chronic cutaneous wounds reveals subregion- and wound type-specific differential gene expression.International wound journal · 2024Article
- Therapeutic Effects of Statins: Promising Drug for Topical and Transdermal Administration.Current medicinal chemistry · 2024Review
- Molecular Pathophysiology of Chronic Wounds: Current State and Future Directions.Cold Spring Harbor perspectives in biology · 2023Review
- KRT17 from skin cells with high glucose stimulation promotes keratinocytes proliferation and migration.Frontiers in endocrinology · 2023Article
- Calreticulin: a multifunctional protein with potential therapeutic applications for chronic wounds.Frontiers in medicine · 2023Review
- Functional drug-delivery hydrogels for oral and maxillofacial wound healing.Frontiers in bioengineering and biotechnology · 2023Review
- The NIDDK Diabetic Foot Consortium.Journal of diabetes science and technology · 2023Article
- Intrinsic Networks Regulating Tissue Repair: Comparative Studies of Oral and Skin Wound Healing.Cold Spring Harbor perspectives in biology · 2022Review
- Article
- Advanced Wound Diagnostics: Toward Transforming Wound Care into Precision Medicine.Advances in wound care · 2022Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The epidermis is maintained by epidermal stem cells (ESCs) that reside in distinct niches and contribute to homeostasis and wound closure. Keratinocytes at the nonhealing edges of venous ulcers (VUs) are healing-incompetent, hyperproliferative, and nonmigratory, suggesting deregulation of ESCs. To date, genes which regulate ESC niches have been studied in mice only. Utilizing microarray analysis of VU nonhealing edges, we identified changes in expression of genes harboring regulation of ESCs and their fate. In a prospective clinical study of 10 VUs, we confirmed suppression of the bone morphogenetic protein receptor (BMPR) and GATA binding protein 3 (GATA3) as well as inhibitors of DNA-binding proteins 2 and 4 (ID2 and ID4). We also found decreased levels of phosphorylated glycogen synthase kinase 3 (GSK3), nuclear presence of β-catenin, and overexpression of its transcriptional target, c-myc, indicating activation of the Wnt pathway. Additionally, we found down-regulation of leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1), a gene important for maintaining ESCs in a quiescent state, and absence of keratin 15 (K15), a marker of the basal stem cell compartment suggesting local depletion of ESCs. Our study shows that loss of genes important for regulation of ESCs and their fate along with activation of β-catenin and c-myc in the VU may contribute to ESC deprivation and a hyperproliferative, nonmigratory healing incapable wound edge.
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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.