Down-regulation of microRNA-142-5p attenuates oxygen-glucose deprivation and reoxygenation-induced neuron injury through up-regulating Nrf2/ARE signaling pathway.
MicroRNAs (miRNAs) play vital roles in regulating neuron survival during cerebral ischemia/reperfusion injury. miR-142-5p is reported to be an important regulator of cellular survival. However, little is known about the role of miR-142-5p in regulating neuron survival during cerebral ischemia/reperfusion injury. In this study, we aimed to investigate the precise function and mechanism of miR-142-5p in the regulation of neuron ischemia/reperfusion injury using a cellular model of oxygen-glucose deprivation and reoxygenation (OGD/R)-induced injury in hippocampal neurons in vitro. We found that miR-142-5p was induced in hippocampal neurons with OGD/R treatment. The inhibition of miR-142-5p attenuated OGD/R-induced cell injury and oxidative stress, whereas the overexpression of miR-142-5p aggravated them. Nuclear factor erythroid 2-related factor 2 (Nrf2) was identified as a target gene of miR-142-5p. Moreover, miR-142-5p regulated Nrf2 expression and downstream signaling. Knockdown of Nrf2 abolished the protective effects of miR-142-5p suppression. In addition, we showed an inverse correlation relationship between miR-142-5p and Nrf2 in an in vivo model of middle cerebral artery occlusion in rats. Taken together, these results suggest that miR-142-5p contributes to OGD/R-induced cell injury and the down-regulation of miR-142-5p attenuates OGD/R-induced neuron injury through promoting Nrf2 expression. Our study provides a novel insight into understanding the molecular pathogenesis of cerebral ischemia/reperfusion injury and indicates a potential therapeutic target for the treatment of cerebral ischemia/reperfusion injury.
Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Ning
N
Wang
Department of Anesthesiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Lingmin
L
Zhang
Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Yang
Y
Lu
Department of Gastroenterology, The Second Affiliated Hospital of The Fourth Military Medical University, Xi'an 710038, China.
Mingxin
M
Zhang
Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Zhenni
Z
Zhang
Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Kui
K
Wang
Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. Electronic address: lvjianruiljr@163.com.
Jianrui
J
Lv
D000818:Animals; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism; D002265:Carboxylic Ester Hydrolases / Q000235:genetics*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics*; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics*
C583884:MIRN142 microRNA, rat; D035683:MicroRNAs; D051267:NF-E2-Related Factor 2; D002265:Carboxylic Ester Hydrolases; C019734:arylesterase; D005947:Glucose; D010100:Oxygen
ARE; Cerebral ischemic/reperfusion injury; Nrf2; miR-142-5p