Epidermal stem cell-derived exosomes alleviate autophagy induced endothelial cell apoptosis through miR200b-3p/ERK pathway in diabetic wounds

Abstract Backgrounds: Diabetic wounds have the characteristics of abnormal inflammatory response, decreased neovascularization, and disturbed microenvironment. Clinical use of epidermal basal cell suspensions promotes chronic wound healing. Further study found that rat Epidermal stem cells (EpiSCs) could promote the angiogenesis of full-thickness wounds in SD rats. The mechanism of the effect of EpiSCs on wound healing warrants further study.Methods: In vivo, EpiSCs were labeled with enhanced green fluorescent protein and then sprayed on dorsal wound of db/db mice. The quality of wound healing was estimated by the residual wound area rate and Hematoxylin and Eosin (H&E) staining. Expression of neovascular markers and collagen formation were elucidated by immunohistochemistry (IHC), immunofluorescence (IF), and MASSOM.In vitro, the supernatant of EpiSCs were ultra-centrifugated to collected exosomes (EpiSC-EXOs). Human umbilical vein endothelial cells (HUVECs) were treated with high glucose and EpiSC-EXOs. miR 200b-3p is identified abundant in EpiSC-EXOs using RNA sequencing. HUVECs were analyzed with apoptosis rate, ROS level, proliferation and mitochondrial membrane potential.Results: In vivo, Epidermal stem cells (EpiSCs) could colonize in wounds, promoting angiogenesis thus accelerating wound healing in diabetic mouse model (db/db mouse). In vitro, EpiSC-EXOs had the ability to reduce apoptosis by downregulating excessive autophagy induced by high-glucose conditions. Furthermore, we found that miR200b-3p rich in EpiSC-EXOs affected the phosphorylation of ERK by targeting SYDE1 to regulate intracellular autophagy levels, thereby reducing vascular endothelial cell apoptosis caused by a high-glucose environment.Conclusions: Collectively, our results verified the effect of EpiSC-EXOs on apoptosis caused by a high-glucose environment in vascular endothelial cells and revealed that its underlying mechanism occurs through the miR200b-3p/SYDE1/RAS/ERK pathway. Our study explains the role of EpiSCs in promoting wound healing in diabetic patients.