RETRACTED ARTICLE:Bone mesenchymal stemcell-derived exosomal microRNA-29b-3p prevents hypoxic-ischemic injury in rat brain byactivating the PTEN-mediated Akt signaling pathway

Abstract

BackgroundMesenchymal stem cells (MSCs) are suspected to exert neuroprotectiveeffects in brain injury, in part through the secretion of extracellular vesicleslike exosomes containing bioactive compounds. We now investigate the mechanismby which bone marrow MSCs (BMSCs)-derived exosomes harboring the smallnon-coding RNA miR-29b-3p protect against hypoxic-ischemic brain injury inrats.MethodsWe 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 isolatedfrom the culture medium of BMSCs. We treated the MCAO rats with BMSC-derivedexosomes in vivo, and likewise the OGD-treated neurons and BMECs in vitro. Wethen measured apoptosis- and angiogenesis-related features using TUNEL and CD31immunohistochemical staining and in vitro Matrigel angiogenesis assays.ResultsThe dual luciferase reporter gene assay showed that miR-29b-3ptargeted the protein phosphatase and tensin homolog (PTEN). miR-29b-3p wasdownregulated and PTEN was upregulated in the brain of MCAO rats and inOGD-treated cultured neurons. MCAO rats and OGD-treated neurons showed promotedapoptosis and decreased angiogenesis, but overexpression of miR-29b-3p orsilencing of PTEN could reverse these alterations. Furthermore, miR-29b-3p couldnegatively regulate PTEN and activate the Akt signaling pathway. BMSCs-derivedexosomes also exerted protective effects against apoptosis of OGD neurons andcell apoptosis in the brain samples from MCAO rats, where we also observedpromotion of angiogenesis.ConclusionBMSC-derived exosomal miR-29b-3p ameliorates ischemic brain injuryby promoting angiogenesis and suppressing neuronal apoptosis, a finding whichmay be of great significance in the treatment of hypoxic-ischemic braininjury.