Exosomes Secreted by Adipose-Derived Stem Cells Contribute to Angiogenesis of Brain Microvascular Endothelial Cells Following Oxygen –Glucose Deprivation In Vitro Through MicroRNA-181b/TRPM7 Axis

In this study, we identified the role of exosomal microRNA-181b-5p (181b-Exos) in regulating post-stroke angiogenesis. The results of migration assay and capillary network formation assay showed that exosomes secreted by ADSCs (ADSCs-Exos) promoted the mobility and angiogenesis of brain microvascular endothelial cells (BMECs) after oxygen-glucose deprivation (OGD). Quantitative real-time polymerase chain reaction (qRT-PCR) showed that microRNA-212-5p (miR-212-5p) and miR-181b-5p were upregulated in BMECs subjected to the brain extract of the middle cerebral artery occlusion rats. The migration distance and tube length were increased in BMECs cultured with 181b-Exos. Furthermore, we identified that transient receptor potential melastatin 7 (TRPM7) was a direct target of miR-181b-5p. TRPM7 mRNA and protein levels were declined in BMECs cultured with 181b-Exos, but not in BMECs cultured with 212-Exos. Overexpression of TRPM7 reversed the effects of 181b-Exos on migration and tube formation of BMECs. In addition, 181b-Exos upregulated the protein expression of hypoxia-inducible factor 1 α and vascular endothelial cell growth factor, and downregulated the protein expression of tissue inhibitor of metalloproteinase 3. The regulatory effect of 181b-Exos was attenuated by overexpressing TRPM7. Altogether, ADSCs-Exos promote the angiogenesis of BMECs after OGD via miR-181b-5p/TRPM7 axi s, suggesting that ADSCs-Exos may represent a novel therapeutic approach for stroke recovery.
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research