title: Inflammation-induced miRNA-155 inhibits self-renewal of neural stem cells via suppression of CCAAT/enhancer binding protein β (C/EBPβ) expression.
abstract: Intracerebral inflammation resulting from injury or disease is implicated in disruption of neural regeneration and may lead to irreversible neuronal dysfunction. Analysis of inflammation-related microRNA profiles in various tissues, including the brain, has identified miR-155 among the most prominent miRNAs linked to inflammation. Here, we hypothesize that miR-155 mediates inflammation-induced suppression of neural stem cell (NSC) self-renewal. Using primary mouse NSCs and human NSCs derived from induced pluripotent stem (iPS) cells, we demonstrate that three important genes involved in NSC self-renewal (Msi1, Hes1 and Bmi1) are suppressed by miR-155. We also demonstrate that suppression of self-renewal genes is mediated by the common transcription factor C/EBPβ, which is a direct target of miR-155. Our study describes an axis linking inflammation and miR-155 to expression of genes related to NSC self-renewal, suggesting that regulation of miR-155 may hold potential as a novel therapeutic strategy for treating neuroinflammatory diseases.
authors.affiliation: Department of Rehabilitation Medicine, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Obora
authors.affiliation: Division of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Onodera
authors.affiliation: Division of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takehara
authors.affiliation: School of Biomedical Engineering, Dalhousie University. Halifax, Nova Scotia, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Frampton
authors.affiliation: Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Joe
authors.initials: J
authors.lastname: Hasei
authors.affiliation: Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ozaki
authors.affiliation: Division of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Teramura
authors.affiliation: Department of Rehabilitation Medicine, Kindai University Faculty of Medicine, Osaka, Japan.|Division of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Kanji
authors.initials: K
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D015415:Biomarkers; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics* / Q000378:metabolism; D000066673:Cell Self Renewal / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics; D000072056:Transcription Factor HES-1 / Q000235:genetics
chemical_list: D015415:Biomarkers; D022782:CCAAT-Enhancer-Binding Protein-beta; D053583:Interleukin-1beta; C524942:MIRN155 microRNA, human; C491297:MSI1 protein, human; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D000072056:Transcription Factor HES-1; C078493:HES1 protein, human