Apoptosis is an important programmed cell death process involved in ischemia/reperfusion injury.MicroRNAs are considered to play an important role in the molecular mechanism underlying the regulation of cerebral ische...Apoptosis is an important programmed cell death process involved in ischemia/reperfusion injury.MicroRNAs are considered to play an important role in the molecular mechanism underlying the regulation of cerebral ischemia and reperfusion injury.However,whether miR-670 can regulate cell growth and death in cerebral ischemia/reperfusion and the underlying mechanism are poorly understood.In this study,we established mouse models of transient middle artery occlusion and Neuro 2a cell models of oxygen-glucose deprivation and reoxygenation to investigate the potential molecular mechanism by which miR-670 exhibits its effects during cerebral ischemia/reperfusion injury both in vitro and in vivo.Our results showed that after ischemia/reperfusion injury,miR-670 expression was obviously increased.After miR-670 expression was inhibited with an miR-670 antagomir,cerebral ischemia/reperfusion injury-induced neuronal death was obviously reduced.When miR-670 overexpression was induced by an miR-670 agomir,neuronal apoptosis was increased.In addition,we also found that miR-670 could promote Yap degradation via phosphorylation and worsen neuronal apoptosis and neurological deficits.Inhibition of miR-670 reduced neurological impairments after cerebral ischemia/reperfusion injury.These results suggest that microRNA-670 aggravates cerebral ischemia/reperfusion injury through the Yap pathway,which may be a potential target for treatment of cerebral ischemia/reperfusion injury.The present study was approved by the Institutional Animal Care and Use Committee of China Medical University on February 27,2017(IRB No.2017PS035K).展开更多
基金supported by the National Natural Science Foundation of China,Nos.81771271(to JF),81902537(to MJY),82001475(to SJY)a Scientific Fund of Shengjing Hospital of China Medical University,No.M0124(to SJY)+1 种基金the“345 Talent Project”from Shengjing Hospital of China Medical University(to SJY)the Natural Science Foundation of Liaoning Province of China,No.20180550913(to MJY).
文摘Apoptosis is an important programmed cell death process involved in ischemia/reperfusion injury.MicroRNAs are considered to play an important role in the molecular mechanism underlying the regulation of cerebral ischemia and reperfusion injury.However,whether miR-670 can regulate cell growth and death in cerebral ischemia/reperfusion and the underlying mechanism are poorly understood.In this study,we established mouse models of transient middle artery occlusion and Neuro 2a cell models of oxygen-glucose deprivation and reoxygenation to investigate the potential molecular mechanism by which miR-670 exhibits its effects during cerebral ischemia/reperfusion injury both in vitro and in vivo.Our results showed that after ischemia/reperfusion injury,miR-670 expression was obviously increased.After miR-670 expression was inhibited with an miR-670 antagomir,cerebral ischemia/reperfusion injury-induced neuronal death was obviously reduced.When miR-670 overexpression was induced by an miR-670 agomir,neuronal apoptosis was increased.In addition,we also found that miR-670 could promote Yap degradation via phosphorylation and worsen neuronal apoptosis and neurological deficits.Inhibition of miR-670 reduced neurological impairments after cerebral ischemia/reperfusion injury.These results suggest that microRNA-670 aggravates cerebral ischemia/reperfusion injury through the Yap pathway,which may be a potential target for treatment of cerebral ischemia/reperfusion injury.The present study was approved by the Institutional Animal Care and Use Committee of China Medical University on February 27,2017(IRB No.2017PS035K).
