Objective: Dishevelled-Axin (DIX) domain containing 1 (DIXDC1), a novel DIX domain-containing protein and a positive regulator of Wingless (Wnt) signaling, has previously been reported to play multiple roles in neurodevelopment and neurological disorders. However, whether DIXDC1 plays a role during cerebral ischemia/reperfusion injury remains unknown. In this study, we investigated the potential role of DIXDC1 in neuronal injury induced by oxygen-glucose deprivation and reoxygenation (OGD/R), an in vitro model of cerebral ischemia/reperfusion injury.
Materials and methods: Neuronal injury was induced by OGD/R treatment. Relative mRNA expression of DIXDC1 was detected by real-time quantitative polymerase chain reaction (RT-qPCR). Protein expression of DIXDC1 and β-catenin was determined by Western blot. Cell viability was examined by the cell counting kit-8 assay. Cell cytotoxicity was detected by the lactate dehydrogenase assay. Cell apoptosis was detected by the caspase-3 activity assay. The activity of Wnt/β-catenin signaling was detected by the luciferase reporter assay.
Results: TWe found that DIXDC1 expression was significantly upregulated in hippocampal neurons following OGD/R treatment. Small interfering RNA-mediated silencing of DIXDC1 significantly impaired viability and promoted cell injury and apoptosis in neurons with OGD/R treatment. In contrast, overexpression of DIXDC1 increased the viability and reduced cell injury and apoptosis in neurons with OGD/R treatment, showing protective effects against OGD/R injury. Furthermore, our results showed that DIXDC1 promoted the expression of β-catenin and activation of Wnt signaling. Notably, inhibition of Wnt signaling significantly abrogated DIXDC-mediated neuroprotective effects.
Conclusions: Our results demonstrate that DIXDC1 prevents OGD/R-induced neuronal injury by promoting Wnt/β-catenin signaling. Our study indicates that DIXDC1 may play an important role in cerebral ischemia and reperfusion serving as a potential target for the treatment of cerebral ischemia/reperfusion injury.