Metabolic reprogramming in skin wound healing

Abstract Metabolic reprogramming refers to the ability of a cell to alter its metabolism in response to different stimuli and forms of pressure. It helps cells resist external stress and provides them with new functions. Skin wound healing involves the metabolic reprogramming of nutrients, such as glucose, lipids, and amino acids, which play vital roles in the proliferation, differentiation, and migration of multiple cell types. During the glucose metabolic process in wounds, glucose transporters and key enzymes cause elevated metabolite levels. Glucose-mediated oxidative stress drives the proinflammatory response and promotes wound healing. Reprogramming lipid metabolism increases the number of fibroblasts and decreases the number of macrophages. It enhances local neovascularization and improves fibrin stability to promote extracellular matrix remodelling, accelerates wound healing, and reduces scar formation. Reprogramming amino acid metabolism affects wound re-epithelialization, collagen deposition, and angiogenesis. However, comprehensive reviews on the role of metabolic reprogramming in skin wound healing are lacking. Therefore, we have systematically reviewed the metabolic reprogramming of glucose, lipids, and amino acids during skin wound healing. Notably, we identified their targets with potential therapeutic value and elucidated their mechanisms of action.