ArticleDiabetologia2023
Reversal of dual epigenetic repression of non-canonical Wnt-5a normalises diabetic corneal epithelial wound healing and stem cells.
Article in Diabetologia, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 25 citations in OpenAlex.
- Systematic Analysis of Stromal-Epithelial Crosstalk Reveals the FGF21-FGFR3 Axis as a Key Driver of Corneal Wound Healing.Investigative ophthalmology & visual science · 2026Article
- Insights into small-molecule neurotransmitter levels and distribution during tissue regeneration in an ear pinna model in mice.Scientific reports · 2026Article
- Targeted AAV6 gene therapy restores corneal endothelial function in three hereditary corneal dystrophies.Cell reports. Medicine · 2026Article
- Lipid-Polymer Nanoparticles (LiPoNs) Mediated Codelivery of AntimiR-21 and Gadolinium Chelate in Triple Negative Breast Cancer Theranostics.Bioengineering (Basel, Switzerland) · 2026Article
- Oxidative stress-regulatory role of miR-10b-5p in the diabetic human cornea revealed through integrated multi-omics analysis.Diabetologia · 2026Article
- Mapping the Landscape of Epigenetic Research in Diabetes Mellitus: A Decade-Long Bibliometric Analysis (2014-2024).Current diabetes reviews · 2026Review
- Research progress on regulatory mechanisms of mucosal barriers and their applications in allergic diseases.Frontiers in immunology · 2026Review
- 4D-printed hydrogel with precise regulation of viability and environment of stem cells for diabetic skin wound healing.Materials today. Bio · 2025Article
- Inhibition of Histone Methyltransferase G9a Activates Autophagy and Provides Protection in Dry Eye Disease.Investigative ophthalmology & visual science · 2025Article
- Alginate formulations with high loads of zebularine and retinoic acid promote tissue growth and innervation and induce extensive epigenetic repatterning.Scientific reports · 2025Article
- Combination Therapy with Human Chorionic Villi MSCs and Secretory Factors Enhances Cutaneous Wound Healing in a Rat Model.International journal of molecular sciences · 2025Article
- Identification of Wnt-5a Receptors Important in Diabetic and Non-Diabetic Corneal Epithelial Wound Healing.Investigative ophthalmology & visual science · 2025Article
- Role of epigenetic regulation in diminished ovarian reserve.Journal of assisted reproduction and genetics · 2025Review
- Evaluating Therapeutic and Chemical Toxicity Using Organ-Cultured Porcine Corneas and Epithelial Wound Healing.Journal of visualized experiments : JoVE · 2025Article
- Role of epigenetics in corneal health and disease.Progress in retinal and eye research · 2025Review
- Discovery Potential Hub Genes and Pathways in Keloid Fibroblast Development Based on Bioinformatics Analysis.International journal of genomics · 2025Article
- Dynamics of DNA methylation during osteogenic differentiation of porcine synovial membrane mesenchymal stem cells from two metabolically distinct breeds.Epigenetics · 2024Article
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Neutrophil pyroptosis regulates corneal wound healing and post-injury neovascularisation.Clinical and translational medicine · 2024Article
- PDIA3 orchestrates effector T cell program by serving as a chaperone to facilitate the non-canonical nuclear import of STAT1 and PKM2.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
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Authors and funding
23 authors at 4 institutions in 4 countries.
Funding
Abstract
aims/hypothesisDiabetes is associated with epigenetic modifications including DNA methylation and miRNA changes. Diabetic complications in the cornea can cause persistent epithelial defects and impaired wound healing due to limbal epithelial stem cell (LESC) dysfunction. In this study, we aimed to uncover epigenetic alterations in diabetic vs non-diabetic human limbal epithelial cells (LEC) enriched in LESC and identify new diabetic markers that can be targeted for therapy to normalise corneal epithelial wound healing and stem cell expression.
methodsHuman LEC were isolated, or organ-cultured corneas were obtained, from autopsy eyes from non-diabetic (59.87±20.89 years) and diabetic (71.93±9.29 years) donors. The groups were not statistically different in age. DNA was extracted from LEC for methylation analysis using Illumina Infinium 850K MethylationEPIC BeadChip and protein was extracted for Wnt phospho array analysis. Wound healing was studied using a scratch assay in LEC or 1-heptanol wounds in organ-cultured corneas. Organ-cultured corneas and LEC were transfected with WNT5A siRNA, miR-203a mimic or miR-203a inhibitor or were treated with recombinant Wnt-5a (200 ng/ml), DNA methylation inhibitor zebularine (1-20 µmol/l) or biodegradable nanobioconjugates (NBCs) based on polymalic acid scaffold containing antisense oligonucleotide (AON) to miR-203a or a control scrambled AON (15-20 µmol/l).
resultsThere was significant differential DNA methylation between diabetic and non-diabetic LEC. WNT5A promoter was hypermethylated in diabetic LEC accompanied with markedly decreased Wnt-5a protein. Treatment of diabetic LEC and organ-cultured corneas with exogenous Wnt-5a accelerated wound healing by 1.4-fold (p<0.05) and 37% (p<0.05), respectively, and increased LESC and diabetic marker expression. Wnt-5a treatment in diabetic LEC increased the phosphorylation of members of the Ca CONCLUSIONS/
interpretationWe provide the first account of epigenetic changes in diabetic corneas including dual inhibition of WNT5A by DNA methylation and miRNA action. Overall, Wnt-5a is a new corneal epithelial wound healing stimulator that can be targeted to improve wound healing and stem cells in the diabetic cornea. DATA AVAILABILITY: The DNA methylation dataset is available from the public GEO repository under accession no. GSE229328 ( https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE229328 ).
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