Exosomal microRNA-150-5p from bone marrow mesenchymal stromal cells mitigates cerebral ischemia/reperfusion injury via targeting toll-like receptor 5.

ABSTRACT

MicroRNA (miR)-150-5p has been investigated in many studies, while the role of exosomal miR-150-5p from bone arrow mesenchymal stromal cells (BMSCs) on cerebral ischemia/reperfusion (I/R) injury is not fully explored. This research aims to probe the effects of exosomal miR-150-5p from BMSCs on cerebral I/R injury via regulating B-cell translocation gene 2 (TLR5). Bone marrow mesenchymal stem cell-derived exosomes (BMSCs-Exo) were isolated and identified. The middle cerebral artery occlusion (MCAO) rat model was established and treated by BMSCs-Exo. Then, functional assays were conducted to explore neurological function, pathological changes, neuron apoptosis and inflammatory factors in MCAO rats. miR-150-5p and TLR5 expression in rat brain tissues were detected. Then, gain and loss-function assays were conducted to determine the impact of exosomes, miR-150-5p and TLR5 on neurological function, pathological changes, neuron apoptosis and inflammatory factors of MCAO rats. The binding relation between miR-150-5p and TLR5 was validated. It was found that miR-150-5p expression was decreased while TLR5 level was augmented in MCAO rats. BMSCs-Exo could improve neurological function, pathological changes, decelerate neuron apoptosis and reduce inflammatory factors in MCAO rats. Enriched miR-150-5pcould enhance the protective effects of BMSCs-Exo on cerebral I/R injury. The elevated TLR5 reversed the impacts of elevated exosomal miR-150-5p on cerebral I/R injury. TLR5 was targeted by miR-150-5p. This research manifested that exosomal miR-150-5p from BMSCs exerts protective effects on cerebral I/R injury via repressing TLR5. This study provided novel therapeutic targets for the treatment of cerebral I/R injury.