miR-21-5p alleviates leakage of injured brain microvascular endothelial barrier in vitro through suppressing inflammation and apoptosis

Our recent researches have identified increased expression of miR-21-5p in rats brain following traumatic brain injury (TBI), which protected against blood-brain barrier (BBB) damage. To further study the mechanism underlying the role of miR-21-5p on alleviating BBB damage after TBI, we performed the scratch injury model on cultured brain microvascular endothelial cells (BMVECs), which formed the microvascular endothelial barrier an integral part of the highly specialized BBB. The expression level of miR-21-5p in BMVECs was observed to be increased after scratch injury, and could be further up regulated by transfecting miR-21-5p mimics. We found that up-regulation of miR-21-5p level in BMVECs can alleviate endothelial barrier damage and loss of tight junction proteins. To further investigate the mechanism of this protective effect, we evaluated the impact of miR-21-5p on inflammation and apoptosis in injured BMVECs. On one hand, miR-21-5p suppressed inflammation by regulating the expression of inflammatory cytokines and NF-kB signaling. On the other hand, miR-21-5p inhibited cellular apoptosis by regulating the expression of apoptosis factors and Akt signaling. In addition, we also detected the activity of Ang-1/Tie-2 axis (associated with BBB stabilization) in BMVECs after scratch injury, and found that miR-21-5p can promote its activation. Taken together, miR-21-5p alleviates leakage of injured brain microvascular endothelial barrier through suppressing inflammation and apoptosis, while impacting the activities of NF-kB, Akt and Ang-1/Tie-2 signaling. Thus, miR-21-5p could be a potential therapeutic target for interventions of BBB damage after TBI. (C) 2016 Published by Elsevier B.V.