Micro RNA-125b (miRNA-125b) function in astrogliosis and glial cell proliferation
Micro RNA-125b (miRNA-125b) function in astrogliosis and glial cell proliferation
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DOI：
10.1016/j.neulet.2010.03.054
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发表时间：
2010-05-26
影响因子：
2.5
通讯作者：
Lukiw, W. J.
中科院分区：
文献类型：
--
作者：
Pogue, A. I.;Cui, J. G.;Lukiw, W. J.
微小RNA（microRNAs，miRNAs）是基因表达的转录后调节因子，调节其靶信使RNA（mRNAs）的稳定性和翻译。在这里，我们报告了人脑富集的miRNA-125 b的水平在白细胞介素-6（IL-6）应激的正常人星形胶质细胞（NHA）中上调，这种治疗已知会诱导星形胶质细胞增生。在体外，将抗miRNA-125 b外源性添加到IL-6应激的NHA培养物中，既减弱了神经胶质细胞增殖，又增加了细胞周期蛋白依赖性激酶抑制剂2A（CDKN 2A）的表达，CDKN 2A是miRNA-125 b靶点和细胞生长的负调节因子。在晚期阿尔茨海默病（AD）和唐氏综合征（DS）脑、与星形胶质细胞增生相关的慢性神经系统疾病中，miRNA-125 b丰度与胶质细胞标志物胶质细胞酸性蛋白（GFAP）和波形蛋白以及CDKN 2A下调之间存在强正相关性。结果表明，miRNA-125 b上调有助于星形胶质细胞增生和细胞周期缺陷，这是脑组织退化的特征。出版社：Elsevier爱尔兰Ltd.
Micro RNAs (miRNAs) are post-transcriptional modulators of gene expression that regulate the stability and translation of their target messenger RNAs (mRNAs). Here we report that the levels of a human brain-enriched miRNA-125b are up-regulated in interleukin-6 (IL-6)-stressed normal human astrocytes (NHA), a treatment known to induce astrogliosis. In vitro, anti-miRNA-125b added exogenously to IL-6-stressed NHA cultures attenuated both glial cell proliferation and increased the expression of the cyclin-dependent kinase inhibitor 2A (CDKN2A), a miRNA-125b target and negative regulator of cell growth. A strong positive correlation between miRNA-125b abundance and the glial cell markers glial fibrillary acidic protein (GFAP) and vimentin, and CDKN2A down-regulation was noted in advanced Alzheimer's disease (AD) and in Down's syndrome (DS) brain, chronic neurological disorders associated with astrogliosis. The results suggest that miRNA-125b up-regulation contributes to astrogliosis and to defects in the cell cycle that are characteristic of degenerating brain tissues. Published by Elsevier Ireland Ltd.