Inflammation-induced miRNA-155 inhibits self-renewal of neural stem cells via suppression of CCAAT/enhancer binding protein \u03b2 (C/EBP\u03b2) expression

Kayoko Obora,John Frampton,Takeshi Teramura,Toshiyuki Takehara,Kanji Fukuda,Joe Hasei,Toshifumi Ozaki,Yuta Onodera

doi:10.1038/srep43604

Kayoko Obora, John Frampton + Show 6 more

Open Access

https://doi.org/10.1038/srep43604

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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.

Highlights

Inflammation is linked to increased neuronal degeneration, neural cell death, altered gene expression profiles and changes in cell physiology in a variety of intractable neurological and cerebrovascular diseases[1,2]
We examine the relationship between miR-155 and stem cell self-renewal in primary mouse neural stem cell (NSC) and human NSCs derived from induced pluripotent stem cells
We examined the effects of exposure to the inflammatory cytokine IL-1βon mouse NSC self-renewal

Summary

Introduction

Inflammation is linked to increased neuronal degeneration, neural cell death, altered gene expression profiles and changes in cell physiology in a variety of intractable neurological and cerebrovascular diseases[1,2]. Exposure to inflammatory signals suppresses self-renewal of NSCs in the adult brain[4,5,6] This loss of neurogenesis is restored by blocking inflammation[4,5], suggesting that there may be an intricate molecular network linking neural inflammation to stem cell renewal in the brain. Elucidating this network may support development of therapeutics for treating diseases associated with neuronal inflammation. We examine the relationship between miR-155 and stem cell self-renewal in primary mouse NSCs and human NSCs derived from induced pluripotent stem (iPS) cells

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