Downregulation of microRNA-302b-3p relieves oxygen-glucose deprivation/re-oxygenation induced injury in murine hippocampal neurons through up-regulating Nrf2 signaling by targeting fibroblast growth factor 15/19

Abstract

MicroRNAs have emerged as critical mediators of cerebral ischaemia/reperfusion injury. Recent studies have demonstrated that microRNA-302b-3p (miR-302b-3p) plays an important role in regulating apoptosis and oxidative stress in various cells. However, whether miR-302b-3p is involved in regulating cerebral ischaemia/reperfusion injury-induced neuronal apoptosis and oxidative stress remains unknown. In the present study, we explored the potential function and molecular mechanism of miR-302b-3p in oxygen-glucose deprivation/re-oxygenation (OGD/R)-induced neuronal injury, using an in vitro model of cerebral ischaemia/reperfusion injury. We found that miR-302b-3p expression was up-regulated by OGD/R treatment in neurons. The inhibition of miR-302b-3p improved cell viability, and reduced apoptosis and the production of reactive oxygen species, showing a protective effect against OGD/R-induced injury. Interestingly, miR-302b-3p was shown to target and modulate murine fibroblast growth factor 15 (FGF15). Moreover, our results showed that miR-302b-3p down-regulation contributed to the promotion of nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE)-mediated antioxidant signaling associated with the inactivation of glycogen synthase kinase-3β. However, the knockdown of FGF15 significantly reversed the miR-302b-3p inhibition-mediated protective effect in OGD/R-treated neurons. Overall, these results demonstrated that miR-302b-3p inhibition confers a neuroprotective effect in OGD/R-treated neurons by up-regulating Nrf2/ARE antioxidant signaling via targeting FGF15, providing a novel target for neuroprotection in cerebral ischaemia/reperfusion injury.

Keywords: Cerebral ischaemia/reperfusion injury; FGF15; GSK-3β; Nrf2.