Potential roles of histone deacetylases in diabetic wound healing

Diabetic foot ulcer is the most prevalent and serious lower-limb complication among individuals with diabetes, and it significantly contributes to the incidence of non-traumatic amputations. The repeated failure of diabetic wounds to heal can result in diabetic foot ulcers, inflicting considerable physical suffering and imposing substantial economic burdens on both patients and global healthcare systems because of the complexity and high costs of treatment. The mechanisms underlying the impaired healing of diabetic wounds are intricate and incompletely understood. Histone deacetylases (HDACs) are critical epigenetic regulators that catalyze the removal of acetyl or acyl groups from lysine residues in proteins, thereby modulating various biological processes, including transcription, apoptosis, and metabolism. Nevertheless, the precise roles of HDACs in diabetic wound healing remain largely unexplored. Thus, the current review describes the pivotal roles of HDACs in diabetic wound healing, focusing on their regulation of inflammatory responses, vascular dysfunction, and epithelial renewal, which are critical events in wound healing. Furthermore, we discuss the therapeutic potential of HDAC inhibitors and propose future directions for clinical application.