MiR-21 involve in ERK-mediated upregulation of MMP9 in the rat hippocampus following cerebral ischemia

Matrix metallinoprotease-9 (MMP9) plays a key role in the pathogenesis of post-ischemic blood brain barrier (BBB) disruption and the formation of lesions after cerebral ischemia. In this study we investigate the effect of brain-specific miRNAs on MMP-9 protein level in the rat hippocampus following cerebral ischemia and its underlying mechanism. Cerebral ischemia significantly upregulated miR-21 and -224 in the hippocampus; however, expression of miR-122 and -338-3p was not significantly affected by ischemia. Silencing of miR-21, but not -224, reduced MMP9 protein level after cerebral ischemia. Downregulation of extracellular signal-regulated kinase (ERK) signaling using the ERK inhibitor U0126 and the calcium-channel blocker ketamine inhibited the upregulation of miR-21 expression and MMP9 protein level after cerebral ischemia. The study suggests that cerebral ischemia up-regulates expression level of miR-21, which is involved in ERK-stimulated upregulation of MMP9 following cerebral ischemia via a calcium-dependent mechanism.

► Cerebral ischemia induces significant up-regulation of miR-21 and -224. ► Gene silence of miR-21 but not -224 can reduce increment of MMP9 protein levels. ► MiR-21 plays an important role in ERK-induced MMP9 expression after ischemia. ► MiR-21 mediated MMP9 up-regulation is closely linked with calcium signal.