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.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Funding
Hebei Provincial Key R&D Program Health Innovation Project (21377706D); the Central Government Guides Local Science and Technology Development Fund, specifically under the Science and Technology Innovation Base Project (Project No. 236Z7756G); and the Medical Science Research Project of Hebei Province (20220243); the Medical Science Research Project of Hebei Province (2024096).
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SWX and LZK contributed to the study conception and design. FYL and LQ performed material preparation, data collection and analysis. The first draft of the manuscript was written by HXH and DYF. DXL commented on previous versions of the manuscript. HXH and LZK confirmed the authenticity of all the raw data. Both authors have read and approved the final manuscript.
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Shi, W., Li, Q., Dong, X. et al. miR-181a-5p of MSCs-derived exosomes promote vascular formation and cell proliferation by PTEN/PI3K/AKT axis in HUVECs. Sci Rep (2026). https://doi.org/10.1038/s41598-026-44672-5
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DOI: https://doi.org/10.1038/s41598-026-44672-5