MicroRNA-30a regulates acute cerebral ischemia-induced blood-brain barrier damage through ZnT4/zinc pathway.

ABSTRACT: The mechanism of early blood-brain barrier (BBB) disruption after stroke has been intensively studied but still not fully understood. Here, we report that microRNA-30a (miR-30a) could mediate BBB damage using both cellular and animal models of ischemic stroke. In the experiments in vitro, inhibition of miR-30a decreased BBB permeability, prevented the degradation of tight junction proteins, and reduced intracellular free zinc in endothelial cells. We found that the zinc transporter ZnT4 was a direct target of negative regulation by miR-30a, and ZnT4/zinc signaling pathway contributed significantly to miR-30a-mediated BBB damage. Consistent with these in vitro findings, treatment with miR-30a inhibitor reduced zinc accumulation, increased the expression of ZnT4, and prevented the loss of ti

SUBMITTER: Wang P 

PROVIDER: S-EPMC7922758 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature