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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Hou, Kun Li, Guichen Zhao, Jinchuan Xu, Baofeng Zhang, Yang Yu, Jinlu Xu, Kan |
| Abstract | Background Mesenchymal stem cells (MSCs) are suspected to exert neuroprotective effects in brain injury, in part through the secretion of extracellular vesicles like exosomes containing bioactive compounds. We now investigate the mechanism by which bone marrow MSCs (BMSCs)-derived exosomes harboring the small non-coding RNA miR-29b-3p protect against hypoxic-ischemic brain injury in rats. Methods We established a rat model of middle cerebral artery occlusion (MCAO) and primary cortical neuron or brain microvascular endothelial cell (BMEC) models of oxygen and glucose deprivation (OGD). Exosomes were isolated from the culture medium of BMSCs. We treated the MCAO rats with BMSC-derived exosomes in vivo, and likewise the OGD-treated neurons and BMECs in vitro. We then measured apoptosis- and angiogenesis-related features using TUNEL and CD31 immunohistochemical staining and in vitro Matrigel angiogenesis assays. Results The dual luciferase reporter gene assay showed that miR-29b-3p targeted the protein phosphatase and tensin homolog (PTEN). miR-29b-3p was downregulated and PTEN was upregulated in the brain of MCAO rats and in OGD-treated cultured neurons. MCAO rats and OGD-treated neurons showed promoted apoptosis and decreased angiogenesis, but overexpression of miR-29b-3p or silencing of PTEN could reverse these alterations. Furthermore, miR-29b-3p could negatively regulate PTEN and activate the Akt signaling pathway. BMSCs-derived exosomes also exerted protective effects against apoptosis of OGD neurons and cell apoptosis in the brain samples from MCAO rats, where we also observed promotion of angiogenesis. Conclusion BMSC-derived exosomal miR-29b-3p ameliorates ischemic brain injury by promoting angiogenesis and suppressing neuronal apoptosis, a finding which may be of great significance in the treatment of hypoxic-ischemic brain injury. |
| Related Links | https://jneuroinflammation.biomedcentral.com/counter/pdf/10.1186/s12974-020-1725-8.pdf |
| Ending Page | 15 |
| Page Count | 15 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 17422094 |
| DOI | 10.1186/s12974-020-1725-8 |
| Journal | Journal of Neuroinflammation |
| Issue Number | 1 |
| Volume Number | 17 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2020-02-03 |
| Access Restriction | Open |
| Subject Keyword | Neurosciences Neurology Neurobiology Immunology Hypoxic-ischemic brain injury microRNA-29b-3p Bone mesenchymal stem cells Angiogenesis Exosome PTEN Akt signaling pathway |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neuroscience Immunology Cellular and Molecular Neuroscience Neurology |
| Journal Impact Factor | 9.3/2023 |
| 5-Year Journal Impact Factor | 9.8/2023 |
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