Inflammation-induced miRNA-155 inhibits self-renewal of neural stem cells via suppression of CCAAT/enhancer binding protein β (C/EBPβ) expression
Autor: | Yuta Onodera, Joe Hasei, Toshifumi Ozaki, Takeshi Teramura, Kanji Fukuda, Toshiyuki Takehara, John P. Frampton, Kayoko Obora |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Interleukin-1beta Nerve Tissue Proteins Biology Article 03 medical and health sciences Mice Neural Stem Cells RNA interference microRNA Animals Humans HES1 Cell Self Renewal Induced pluripotent stem cell Transcription factor Regulation of gene expression Inflammation Multidisciplinary Ccaat-enhancer-binding proteins CCAAT-Enhancer-Binding Protein-beta RNA-Binding Proteins Neural stem cell Cell biology MicroRNAs 030104 developmental biology Gene Expression Regulation Transcription Factor HES-1 RNA Interference Biomarkers |
Zdroj: | Scientific Reports |
ISSN: | 2045-2322 |
Popis: | 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. |
Databáze: | OpenAIRE |
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