MiR-7 involves the activation of Nrf2 pathway by targeting Keap1 in epileptic seizure

MicroRNAs (miRNAs) are increasingly recognized as diagnostic biomarkers of epileptogenesis as well as targets to prevent or disrupt epilepsy. Keap1, a cytoplasmic inhibitory protein called Kelch-like ECH-associated protein 1, is also reported associated with epilepsy. However, the possible involvement of miRNAs in Keap1-mediated molecular basis for protection from epileptic seizure-induced brain damage is less understood. In the present study, Wistar rats were rapidly kindled in the amygdala. We found a dramatic upregulation of miR-7 and downregulation of Keap1 in the hippocampus of kindled rats, compared with control and sham group. Moreover, luciferase reporter gene assays identified that miR-7 was able to target 3'-untranslated region (3'-UTR) of Keap1 mRNA. To investigate the role of miR-7 in the protection of epilepsy mediated by Keap1/Nrf2 pathway, we used a transfection approach to overexpress miR-7, and then detected a consequential decrease in Keap1 mRNA and protein which subsequently results in an increased Nrf2 expression and cytoprotective enzymes (HO-1 and NQO1) expression. These results indicate that miR-7 may involve the protection of protection through targeting Keap1 and the subsequent activation of Nrf2 pathway.