Retracted: Bone marrow mesenchymal stem cells-derived extracellular vesicles carrying microRNA-221-3p protect against ischemic stroke via ATF3

Abstract

Objective: We aim to explore the protective effect of bone marrow mesenchymal stem cells (BMSCs)-derived exosomal microRNA-221-3p (miR-221-3p) on ischemic stroke (IS) by targeting activating transcription factor 3 (ATF3).

Methods: The middle cerebral artery occlusion (MCAO) mice model and oxygen-glucose deprivation (OGD) neuron model were established. Extracellular vesicles were isolated from BMSCs (BMSC-EVs) and transfected with altered miR-221-3p or ATF3 to treat the MCAO mice and OGD-treated neurons. MiR-221-3p and ATF3 expression were determined, and the contents of inflammatory factors were detected. The pathological changes and apoptosis in mice brain tissues were observed. In cellular experiments, the viability and apoptosis of OGD-treated neurons were evaluated. Binding relationship between miR-221-3p and ATF3 was determined.

Results: MiR-221-3p was down-regulated and ATF3 was up-regulated in MCAO mice and OGD-treated neurons. BMSC-EVs and BMSC-EVs carrying up-regulated miR-221-3p attenuated inflammation, pathological changes and apoptosis in MCAO mice brain tissues, and also promoted viability and repressed apoptosis of OGD-treated neurons. ATF3 was verified as a target of miR-221-3p.

Conclusion: BMSC-EVs carrying miR-221-3p protect against IS by inhibiting ATF3. This study may be helpful for exploring therapeutic strategies of IS.

Keywords: Activating; Bone marrow mesenchymal stem cells-derived extracellular vesicles; Ischemic stroke; MicroRNA-221-3p; Middle cerebral artery occlusion; Transcription factor 3.