miRNAs-19b, -29b-2* and -339-5p show an early and sustained up-regulation in ischemic models of stroke.
miRNAs-19b, -29b-2* and -339-5p show an early and sustained up-regulation in ischemic models of stroke.
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DOI：
10.1371/journal.pone.0083717
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Bushell M
中科院分区：
文献类型：
--
作者：
Dhiraj DK;Chrysanthou E;Mallucci GR;Bushell M
中风是脑缺血性损伤后神经元的损失，是全球死亡和残疾的主要原因之一。尽管其患病率和严重性，目前的治疗是非常有限的，突出了进一步了解缺血诱导的神经元细胞死亡的分子事件的重要性。缺血区域可细分为两个独立的病理生理区域：快速死亡的坏死核心和潜在可挽救的凋亡半暗带。了解发生在凋亡缺血半暗带的分子事件可能会更深入地了解控制这种可挽救组织的机制。已知miRNA在许多病理条件下的基因表达调控中具有关键作用，包括中风中不同途径的调节。然而，以前的研究已经在整个缺血性梗死中描述了miRNA，并且没有区分坏死核心与凋亡半暗带中的miRNA调节。我们询问在可挽救的凋亡半影区中是否存在缺血损伤后差异调节的独特miRNA。在细胞凋亡诱导之前，使用三血管闭塞方法，在来自体内中风模型的整个梗塞中，与缺血半暗带的体外模型比较miRNA表达谱。在每个系统中，发现多个miRNA在缺血损伤后受到差异调节。然而，miR-19 b、miR-29 b-2* 和miR-339- 5 p在两种模型系统中均显著上调。此外，我们证实了这些结果在神经母细胞瘤细胞系受到半影样缺血性损伤，诱导凋亡细胞死亡途径。数据显示，miR-19 b、miR-29 b-2* 和miR-339- 5 p在缺血损伤后上调，并且可能调节基因表达以控制可挽救的缺血半暗带中的重要细胞途径。对它们的作用和mRNA靶点的进一步研究可能会导致对可挽救的凋亡半影区发生的分子机制的新见解。
Stroke, the loss of neurons after ischemic insult to the brain, is one of the leading causes of death and disability worldwide. Despite its prevalence and severity, current therapy is extremely limited, highlighting the importance of further understanding the molecular events underlying ischemia-induced neuronal cell death. An ischemic area can be subdivided into two separate pathophysiological regions: the rapidly dying necrotic core, and the potentially salvageable apoptotic penumbra. Understanding molecular events occurring in the apoptotic ischemic penumbra may give greater insight into mechanisms controlling this salvageable tissue. miRNAs are known to have key roles in the regulation of gene expression in numerous pathological conditions, including the modulation of distinct pathways in stroke. However, previous studies have profiled miRNAs in the whole ischemic infarct, and do not differentiate between miRNA regulation in the necrotic core versus the apoptotic penumbra. We asked if there were unique miRNAs that are differentially regulated following ischemic insults in the salvageable apoptotic penumbra. miRNA expression profiles were compared in the whole infarct from in vivo stroke models, using the three vessel occlusion approach, to an in vitro model of the ischemic penumbra, prior to apoptotic induction. Multiple miRNAs were found to be differentially regulated following ischemic insults in each system. However, miR-19b, miR-29b-2* and miR-339-5p were significantly up-regulated in both model systems. Further, we confirmed these results in a neuroblastoma cell line subjected to a penumbra-like ischemic insult that induced the apoptotic cell death pathway. The data show that miR-19b, miR-29b-2* and miR-339-5p are up-regulated following ischemic insults and may be regulating gene expression to control important cellular pathways in the salvageable ischemic penumbra. Further investigation of their role and mRNA target identification may lead to new insights into the molecular mechanisms taking place in the salvageable apoptotic penumbra.
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DOI：
10.1038/jcbfm.2008.157
发表时间：
2009-04
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
--
作者：
通讯作者：
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影响因子：
6.3
作者：
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影响因子：
64.5
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Eulalio, Ana;Huntzinger, Eric;Izaurralde, Elisa
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Izaurralde, Elisa
DOI：
10.1093/jnen/62.4.329
发表时间：
2003-04-01
影响因子：
3.2
作者：
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通讯作者：
Planas, AM
DOI：
10.1097/00004647-199803000-00002
发表时间：
1998-03-01
影响因子：
6.3
作者：
Endres, H;Namura, S;Moskowitz, MA
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Moskowitz, MA