Vinexin- deficiency protects against cerebral ischaemia/reperfusion injury by inhibiting neuronal apoptosis

摘要

Vinexin- is an adaptor protein that regulates cell adhesion, cytoskeletal organization and signal transduction. Our previous work showed that Vinexin- protects against cardiac hypertrophy. However, its function in stroke is largely unknown. In the present study, we observed a significant increase in Vinexin- expression in both human intracerebral haemorrhage and mouse cerebral ischaemia/reperfusion (I/R)injury model, indicating that Vinexin- is involved in stroke. Next, using Vinexin- knockout mice, we further demonstrated that Vinexin- deficiency significantly protected against cerebral I/R injury, as demonstrated by a dramatic decrease in the infarct volume and an improvement in neurological function. Additionally, immunofluorescence and western blotting showed that the deletion of Vinexin- attenuated neuronal apoptosis. Mechanically, we found that Akt signalling was up-regulated in the brains of the Vinexin- knockout mice compared with those of the WT control mice after ischaemic injury. Taken together, our results demonstrate that the deletion of Vinexin- potently protects against ischaemic injury by inhibiting neuronal apoptosis, and this effect may occur via the up-regulation of Akt signalling. Our findings revealed that Vinexin- acts as a novel modulator of ischaemic injury, suggesting that Vinexin- may represent an attractive therapeutic target for the prevention of stroke.