ArticleEBioMedicine2019
Epigenetic inhibitor zebularine activates ear pinna wound closure in the mouse.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Insights into small-molecule neurotransmitter levels and distribution during tissue regeneration in an ear pinna model in mice.Scientific reports · 2026Article
- Approaching Scarless Wound Healing: From Passive Anti-Fibrotic to Proactive and Programmable Pro-Regenerative Strategies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Alginate formulations with high loads of zebularine and retinoic acid promote tissue growth and innervation and induce extensive epigenetic repatterning.Scientific reports · 2025Article
- Identification of compounds to promote diabetic wound healing based on transcriptome signature.Frontiers in pharmacology · 2025Article
- Chemotherapy-Mediated Complications of Wound Healing: An Understudied Side Effect.Advances in wound care · 2024Review
- Review
- Reversal of dual epigenetic repression of non-canonical Wnt-5a normalises diabetic corneal epithelial wound healing and stem cells.Diabetologia · 2023Article
- Decoding the Human Epidermal Complexity at Single-Cell Resolution.International journal of molecular sciences · 2023Review
- Release systems based on self-assembling RADA16-I hydrogels with a signal sequence which improves wound healing processes.Scientific reports · 2023Article
- Examination of epigenetic inhibitor zebularine in treatment of skin wounds in healthy and diabetic mice.Journal of tissue engineering and regenerative medicine · 2022Article
- Genome-wide DNA hypermethylation opposes healing in patients with chronic wounds by impairing epithelial-mesenchymal transition.The Journal of clinical investigation · 2022Article
- Combination of mesenchymal stem cells and three-dimensional collagen scaffold preserves ventricular remodeling in rat myocardial infarction model.World journal of stem cells · 2022Article
- Regenerative Drug Discovery Using Ear Pinna Punch Wound Model in Mice.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Zebularine protects against blood-brain-barrier (BBB) disruption through increasing the expression of zona occludens-1 (ZO-1) and vascular endothelial (VE)-cadherin.Bioengineered · 2022Article
- Epigenetic-Based Therapy-A Prospective Chance for Medulloblastoma Patients' Recovery.International journal of molecular sciences · 2021Review
- Imunofan-RDKVYR Peptide-Stimulates Skin Cell Proliferation and Promotes Tissue Repair.Molecules (Basel, Switzerland) · 2020Article
Corrections and comments
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Authors and funding
22 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMost studies on regenerative medicine focus on cell-based therapies and transplantations. Small-molecule therapeutics, though proved effective in different medical conditions, have not been extensively investigated in regenerative research. It is known that healing potential decreases with development and developmental changes are driven by epigenetic mechanisms, which suggests epigenetic repression of regenerative capacity.
methodsWe applied zebularine, a nucleoside inhibitor of DNA methyltransferases, to stimulate the regenerative response in a model of ear pinna injury in mice.
findingsWe observed the regeneration of complex tissue that was manifested as improved ear hole repair in mice that received intraperitoneal injections of zebularine. Six weeks after injury, the mean hole area decreased by 83.2 ± 9.4% in zebularine-treated and by 43.6 ± 15.4% in control mice (p < 10
interpretationThis study is the first to demonstrate an effective induction of complex tissue regeneration in adult mammals using zebularine. We showed that the synergistic action of an epigenetic drug (zebularine) and a transcriptional activator (retinoic acid) could be effectively utilized to induce the regenerative response, thus delineating a novel pharmacological strategy for regeneration. The strategy was effective in the model of ear pinna regeneration in mice, but zebularine acts on different cell types, therefore, a similar approach can be tested in other tissues and organs.
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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.