Year: 2025
Type: article
Abstract: Diabetic neuropathy (DN) and impaired wound healing in diabetic foot ulcers (DFUs) are major complications of diabetes mellitus, driven by complex molecular mechanisms, including epigenetic modifications. Recent research highlights the role of epigenetic markers including DNA methylation, histone modifications, and non-coding RNAs in regulating inflammatory responses, neuronal degeneration, and tissue repair. This review explores the epigenetics of DN and DFUs, emphasizing key regulatory pathways that influence disease progression and wound healing outcomes. Genome-wide DNA methylation studies reveal accelerated epigenetic aging and metabolic memory effects in DN, contributing to sensory neuron dysfunction and neuropathic pain. Epigenetic dysregulation of inflammatory mediators such as Toll-like receptors and the Nod-like receptor family, pyrin domain-containing 3 inflammasome further exacerbates neuronal damage and delays wound healing. Additionally, histone deacetylases play a pivotal role in oxidative stress regulation via the Nrf2 pathway, which is critical for both neuronal protection and angiogenesis in DFUs. Non-coding RNAs, particularly microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs, are emerging as central regulators of the epigenetic crosstalk between DN and DFUs. Several miRNAs, including miR-146a-5p and miR-518d-3p, are implicated in neuropathy severity, while lncRNAs such as nuclear enriched abundant transcript 1 modulate angiogenesis and wound repair. Cellular reprogramming of DFU fibroblasts has also been shown to induce pro-healing miRNA signatures, offering potential therapeutic avenues. Furthermore, recent whole-genome and transcriptomic analyses of DFU-derived monocytes and Charcot foot lesions reveal unique epigenetic signatures that may serve as biomarkers for early detection and personalized interventions. This epigenetic interplay between DN and DFU pathogenesis not only enhances our knowledge of disease mechanisms but also opens avenues for targeted epigenetic therapies to improve clinical outcomes.
Source: World Journal of Diabetes
Authors: Kamaldeen Olalekan Sanusi, Jerome Ndudi Asiwe, Fatimo Ajoke Sulaimon, Farida Bashar, Suleiman Kolawole Yusuf, Hawau Olaide Abdulkadir
Language: English
Topic: Wound Healing and Treatments
Subfield: Rehabilitation
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4416235293