miR-181a-5p of MSCs-derived exosomes promote vascular formation and cell proliferation by PTEN/PI3K/AKT axis in HUVECs

Abstract

Abstract Our previous studies have demonstrated that exosomes play a crucial role in promoting vaginal tissue reconstruction in rats. The present study aims to elucidate the molecular mechanisms through which human umbilical cord mesenchymal stem cell-derived exosomes (hUMSC-Exos), which carry microRNA-181a-5p (miR-181a-5p), promote vascularization and tissue regeneration, with particular focus on the involvement of the PTEN/PI3K/AKT signaling pathway. Human umbilical vein endothelial cells (HUVECs) served as a model for studying angiogenesis and cell proliferation, and the expression levels of miR-181a-5p, PTEN, phospho-PI3K (p-PI3K), and phospho-AKT (p-AKT) were analyzed. HUVECs were transfected with PTEN overexpression vector or a negative control vector, then treated with exosomes derived from mesenchymal stem cells (MSCs) transfected with either a miR-181a-5p mimic or an inhibitor. Cell proliferation and migration were assessed using the Cell Counting Kit-8 and scratch assay, respectively, while cell invasion was evaluated via Transwell assay. The StarBase tool was employed to predict binding sites between miR-181a-5p and its target gene, the phosphatase and tensin homolog (PTEN). This interaction was subsequently validated using a dual-luciferase reporter assay. In HUVECs, elevated miR-181a-5p levels were positively correlate with reduced PTEN expression. In vitro experiments demonstrate that hUMSC-Exos enhance HUVEC migration, proliferation, and tube formation. Furthermore, overexpression of PTEN partially counteracted these miR-181a-5p-mediated effects. Our findings indicate that hUMSC-Exos contain miR-181a-5p, which may enhance tube formation and proliferation in HUVECs by regulating PTEN expression, thereby influencing the PI3K/AKT pathway.