Abstract

Diabetic patients face delayed wound healing due to angiogenesis dysfunction. This study aims to investigate the function of endothelial progenitor cell (EPC)-derived extracellular vesicles (EVs) in wound healing of diabetic mice, providing a theoretical basis for treating difficult-to-heal diabetic wounds. The full-thickness skin wound model was used as an animal model. After treatment with EPC-EVs, wound healing and histopathological structures were evaluated. Peripheral blood was collected to analyze circulating EPCs. In cell models, EV endocytosis, cell viability, angiogenic capacity, and cell migration were detected. miR-204-5p, lncRNA SNHG1, EIF4A3, and HDAC6 were detected. EVs derived from EPCs with miR-204-5p overexpression were extracted to investigate their effects on wound healing. The bindings between miR-204-5p and SNHG1, SNHG1 and EIF4A3, and EIF4A3 and HDAC6 mRNA were validated. EPC-EVs promoted wound healing in diabetic mice. EPC-EVs enhanced angiogenesis and migration in cell models. EPC-EVs with miR-204-5p overexpression exhibited better therapeutic effects. EPC-EVs delivered miR-204-5p into tissues/cells to lower SNHG1 expression. SNHG1 bound to EIF4A3 to increase HDAC6 expression. SNHG1/HDAC6 overexpression partly reversed the pro-angiogenic effects of EPC-EVs on diabetic wound healing and HG-impaired endothelial cells. In conclusion, EPC-EVs enhance EPC mobilization and angiogenesis to accelerate wound repair in diabetic mice via the miR-204-5p/SNHG1/HDAC6 axis.