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.
Sci Rep. 2017 Feb 27;7:43604. doi: 10.1038/srep43604.
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.
脑内炎症由损伤或疾病引起，与神经再生中断有关，并可能导致不可逆的神经元功能障碍。对包括大脑在内的各种组织中与炎症相关的 microRNA 谱进行分析，确定了 miR-155 是与炎症最相关的 miRNA 之一。在这里，我们假设 miR-155 介导炎症诱导的神经干细胞 (NSC) 自我更新抑制。使用原代小鼠 NSCs 和源自诱导多能干细胞 (iPS) 的人 NSCs，我们证明了三个与 NSC 自我更新相关的重要基因（Msi1、Hes1 和 Bmi1）受到 miR-155 的抑制。我们还证明，自我更新基因的抑制是由共同的转录因子 C/EBPβ介导的，C/EBPβ是 miR-155 的直接靶标。我们的研究描述了一条将炎症与 miR-155 联系起来的轴，与 NSC 自我更新相关的基因表达有关，表明 miR-155 的调节可能是治疗神经炎症性疾病的一种新的治疗策略。
