Communication between fibroblasts and endothelial cells is essential for skin wound repair and regeneration. Extracellular vesicles (EVs) are crucial for intracellular communication by transporting active molecules. However, whether EVs derived from diabetic fibroblasts can perform the nomal communication function is unclear. Here, we compared the effects of EVs from human skin fibroblasts (HSFs) induced with or without HG on the angiogenic function of endothelial cells and wound healing.
We first collected EVs from HSFs cultured with normal glucose concentration (NG-EVs) or with HG concentration (HG-EVs) and applied them to treat human umbilical vein endothelial cells (HUVECs). The cells were divided into three groups: control group, NG-EVs group, and HG-EVs group. We then examined the proliferation, migration, apoptosis, and tube formation of HUVECs. To illustrate the mechanism, the expression of β-catenin, GSK-3β, and p-GSK-3β was detected by western-blot. Finally, NG-EVs or HG-EVs were used to treat the wounds of mice to determine their role in wound closure.
By DNA content detection, Annexin V/PI staining, and EdU staining, we found that NG-EVs promoted HUVEC proliferation, while HG-EVs exhibited an opposite effect (
NG-EVs and HG-EVs exert opposite effects on wound healing and angiogenesis possibly by regulating GSK-3β/β-catenin signaling pathway. This research may provide a new treatment strategy for wound healing and illustrate the mechanism for impaired angiogenesis in diabetics.