MicroRNAs Induced During Ischemic Preconditioning

Abstract

BACKGROUND AND PURPOSE: MicroRNAs (miRNA) are single-stranded short RNA molecules that regulate gene expression by either degradation or translational repression of mRNA. Although miRNAs control a number of conditions and diseases, few neuroprotective miRNAs have been described. In this study, we investigated neuroprotective miRNAs induced early in ischemic preconditioning. METHODS: Ischemic preconditioning or focal cerebral ischemia was induced in mice by transient occlusion of the middle cerebral artery for 15 or 120 minutes. We prepared RNA samples from the ischemic cortex at 3 or 24 hours after the onset of ischemia. Selective miRNAs then were synthesized and transfected into Neuro-2a cells before oxygen-glucose deprivation. RESULTS: We detected a total of 360 miRNAs. Two miRNA families, miR-200 and miR-182, were selectively upregulated at 3 hours after ischemic preconditioning. Transfections of some of these were neuroprotective in in vitro ischemia. Among them, miR-200b, miR-200c, and miR-429 targeted prolyl hydroxylase 2 and had the best neuroprotective effect. CONCLUSIONS: Two miRNA families, miR-200 and miR-182, were upregulated early after ischemic preconditioning and the miR-200 family was neuroprotective mainly by downregulating prolyl hydroxylase 2 levels. These miRNAs may be useful in future research and therapeutic applications.