Astragaloside IV promotes exosome secretion of endothelial progenitor cells to regulate PIK3R2/SPRED1 signaling and inhibit pyroptosis of diabetic endothelial cells

Background aims: Treating chronic non-healing diabetic wounds and achieving complete skin regeneration has always been a critical clinical challenge. Methods: In order to address this issue, researchers conducted a study aiming to investigate the role of miR126-3p in regulating the downstream gene PIK3R2 and promoting diabetic wound repair in endothelial progenitor cell (EPC)-derived extracellular vesicles. The study involved culturing EPCs with astragaloside IV, transfecting them with miR-126-3p inhibitor or mock plasmid, interfering with high glucose-induced damage in human umbilical vein endothelial cells (HUVECs) and treating diabetic skin wounds in rats. Results: The healing of rat skin wounds was observed through histological staining. The results revealed that treatment with miR-126-3p-overexpressing EPC-derived extracellular vesicles accelerated the healing of rat skin wounds and resulted in better tissue repair with slower scar formation. In addition, the transfer of EPCderived extracellular vesicles with high expression of miR-126-3p to high glucose-damaged HUVECs increased their proliferation and invasion, reduced necrotic and apoptotic cell numbers and improved tube formation. In this process, the expression of angiogenic factors vascular endothelial growth factor (VEGF)A, VEGFB, VEGFC, basic fibroblast growth factor and Ang -1 significantly increased, whereas the expression of caspase-1, NRLP3, interleukin-1b, inteleukin-18, PIK3R2 and SPRED1 was suppressed. Furthermore, miR126-3p was able to target and inhibit the expression of the PIK3R2 gene, thereby restoring the proliferation and migration ability of high glucose-damaged HUVEC. Conclusions: In summary, these research findings demonstrate the important role of miR-126-3p in regulating downstream genes and promoting diabetic wound repair, providing a new approach for treating chronic non-healing diabetic wounds. (c) 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.