title: MiR-124 contributes to M2 polarization of microglia and confers brain inflammatory protection via the C/EBP-α pathway in intracerebral hemorrhage.
abstract: Microglia mediated inflammation contributes to intracerebral hemorrhage (ICH) induced secondary injury. Activated microglia has dual functions as pro-inflammatory (M1) and anti-inflammatory (M2) factors in brain injury and repair. MiR-124 is a potent anti-inflammatory agent which affects microglia after brain injury. However, the potential of modulating the M1/M2 polarization of microglia after ICH has not been reported. In this experiment, we detected the effect of miR-124 on the M1/M2 polarization state. In addition, the ability miR-124 to subsequently impacted neurological deficit and cerebral water content of ICH mice were studied. Furthermore, the relationship between miR-124 and C/EBP-α target was detected. We found that miR-124 significantly increased in M2-polarized microglia. Transduction of miR-124 mimics decreased proinflammatory cytokine levels. A coculture model of microglia and neuron indicated that M2-polarized microglia protected neuron damage. Furthermore, miR-124 banded to the 3-untranslated region of C/EBP-α and downregulated its protein levels. In vivo, infusion of miR-124 decreased brain levels of C/EBP-α and significantly reduced brain injury in ICH mice. Thus, miR-124 ameliorated ICH-induced inflammatory injury by modulating microglia polarization toward the M2 phenotype via C/EBP-α. MiR-124 regulatory mechanisms also might represent new therapeutic strategy in ICH.
authors.affiliation: Department of Emergency, The First Affiliated Hospital of Zunyi Medical College, Guizhou, 563003, China.
authors.forename: Anyong
authors.initials: A
authors.lastname: Yu
authors.affiliation: Department of Emergency, The First Affiliated Hospital of Zunyi Medical College, Guizhou, 563003, China.
authors.forename: Tianxi
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Emergency, The First Affiliated Hospital of Zunyi Medical College, Guizhou, 563003, China.
authors.forename: Haizhen
authors.initials: H
authors.lastname: Duan
authors.affiliation: Department of Emergency, The First Affiliated Hospital of Zunyi Medical College, Guizhou, 563003, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Emergency, The First Affiliated Hospital of Zunyi Medical College, Guizhou, 563003, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Emergency, The First Affiliated Hospital of Zunyi Medical College, Guizhou, 563003, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical, University, Chongqing, 402160, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical, University, Chongqing, 402160, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical, University, Chongqing, 402160, China. Electronic address: yangzhao5140@sohu.com.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D015415:Biomarkers; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism*; D002543:Cerebral Hemorrhage / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004660:Encephalitis / Q000209:etiology* / Q000378:metabolism* / Q000517:prevention & control; D015870:Gene Expression; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D017628:Microglia / Q000276:immunology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D015415:Biomarkers; D022763:CCAAT-Enhancer-Binding Protein-alpha; D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein
keywords: C/EBP-α; ICH; Inflammation; M2 polarization; Microglia; miR-124