Al Madhoun A. Epigenetics and diabetic wound healing: Wilms tumor 1-associated protein as a therapeutic target. World J Diabetes 2025; 16(6): 105615 [DOI: 10.4239/wjd.v16.i6.105615]
Corresponding Author of This Article
Ashraf Al Madhoun, PhD, Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Jassim AlBahar Street, Dasman 15400, Kuwait. ashraf.madhoun@dasmaninstitute.org
Research Domain of This Article
Medicine, Research & Experimental
Article-Type of This Article
Editorial
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Diabetes. Jun 15, 2025; 16(6): 105615 Published online Jun 15, 2025. doi: 10.4239/wjd.v16.i6.105615
Epigenetics and diabetic wound healing: Wilms tumor 1-associated protein as a therapeutic target
Ashraf Al Madhoun
Ashraf Al Madhoun, Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman 15400, Kuwait
Author contributions: Al Madhoun A designed the overall concept, reviewed literature, wrote, and edited the manuscript.
Supported by the Kuwait Foundation for the Advancement of Sciences and Dasman Diabetes Institute, No. RACB-2021-007.
Conflict-of-interest statement: The author reports no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ashraf Al Madhoun, PhD, Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Jassim AlBahar Street, Dasman 15400, Kuwait. ashraf.madhoun@dasmaninstitute.org
Received: January 30, 2025 Revised: April 3, 2025 Accepted: May 12, 2025 Published online: June 15, 2025 Processing time: 134 Days and 20.3 Hours
Abstract
In this editorial, we highlight the study by Xiao et al. Despite progress in the management of diabetic foot ulcers (DFUs), impaired wound healing remains a significant clinical challenge. Recent studies have highlighted the critical role of epigenetic modifications in diabetic wound healing, with particular emphasis on DNA and RNA methylation pathways. This editorial discusses the findings of Xiao et al, who identified the Wilms tumor 1-associated protein (WTAP) - DNA methyltransferase 1 (DNMT1) axis as a pivotal regulator of endothelial dysfunction in DFUs. WTAP, a regulatory subunit of N6-methyladenosine (m6A) methyltransferase, is upregulated under high-glucose conditions and drives the excessive expression of DNMT1 via m6A modification. This contributes to impaired angiogenesis, reduced cell viability, and delayed wound closure. WTAP knockdown restored endothelial function and significantly improved wound healing in a diabetic mouse model. Furthermore, DNMT1 overexpression abrogated the benefits of WTAP suppression, confirming its downstream effector role. Thus, targeting the WTAP-DNMT1 axis provides a new avenue for DFU management. Moreover, epigenetic interventions that modulate both the m6A and RNA methylation pathways could restore endothelial function and enhance tissue repair in patients with diabetes.
Core Tip: Xiao et al identified the Wilms tumor 1-associated protein (WTAP)-DNA methyltransferase 1 (DNMT1) axis as a pivotal regulator of diabetic foot ulcer healing. Using human umbilical vein endothelial cells and a diabetic mouse model, those researchers demonstrated that WTAP knockdown restored endothelial cell function and enhanced angiogenesis and collagen deposition. Importantly, siRNA-mediated WTAP depletion markedly improved wound closure in the diabetic mice. Furthermore, DNMT1 reversed the beneficial effects of WTAP knockdown, confirming that it is a key downstream effector of WTAP.
