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miR-146a 的表达模式,一种与炎症相关的 microRNA,在实验性和人类颞叶癫痫中的研究。

Expression pattern of miR-146a, an inflammation-associated microRNA, in experimental and human temporal lobe epilepsy.

机构信息

Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, The Netherlands.

出版信息

Eur J Neurosci. 2010 Mar;31(6):1100-7. doi: 10.1111/j.1460-9568.2010.07122.x. Epub 2010 Feb 26.

DOI:10.1111/j.1460-9568.2010.07122.x
PMID:20214679
Abstract

Increasing evidence supports the involvement of inflammatory and immune processes in temporal lobe epilepsy (TLE). MicroRNAs (miRNA) represent small regulatory RNA molecules that have been shown to act as negative regulators of gene expression controlling different biological processes, including immune-system homeostasis and function. We investigated the expression and cellular distribution of miRNA-146a (miR-146a) in a rat model of TLE as well as in human TLE. miR-146a analysis in rat hippocampus was performed by polymerase chain reaction and immunocytochemistry at 1 week and 3-4 months after induction of status epilepticus (SE). Prominent upregulation of miR-146a activation was evident at 1 week after SE and persisted in the chronic phase. The miR-146a expression was confirmed to be present in reactive astrocytes. In human TLE with hippocampal sclerosis, increased astroglial expression of miR-146a was observed mainly in regions where neuronal cell loss and reactive gliosis occurred. The increased and persistent expression of miR-146a in reactive astrocytes supports the possible involvement of miRNAs in the modulation of the astroglial inflammatory response occurring in TLE and provides a target for future studies aimed at developing strategies against pro-epileptogenic inflammatory signalling.

摘要

越来越多的证据支持炎症和免疫过程参与颞叶癫痫(TLE)。microRNAs(miRNA)是小的调节 RNA 分子,已被证明作为基因表达的负调节剂,控制包括免疫系统稳态和功能在内的不同生物学过程。我们研究了 miR-146a(miR-146a)在 TLE 大鼠模型以及人类 TLE 中的表达和细胞分布。通过聚合酶链反应和免疫细胞化学在诱导癫痫持续状态(SE)后 1 周和 3-4 个月时对大鼠海马体中的 miR-146a 进行分析。SE 后 1 周明显上调 miR-146a 激活,并在慢性期持续存在。证实 miR-146a 表达存在于反应性星形胶质细胞中。在伴有海马硬化的人类 TLE 中,观察到 miR-146a 在星形胶质细胞中的表达增加,主要发生在神经元细胞丢失和反应性神经胶质增生的区域。反应性星形胶质细胞中 miR-146a 的增加和持续表达支持 miRNA 可能参与 TLE 中星形胶质细胞炎症反应的调节,并为旨在开发针对致痫性炎症信号的策略的未来研究提供了一个靶标。

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