A transcriptional role for C/EBP β in the neuronal response to axonal injury
A transcriptional role for C/EBP β in the neuronal response to axonal injury
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DOI：
10.1016/j.mcn.2005.04.004
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发表时间：
2005-08-01
影响因子：
3.5
通讯作者：
Miller, FD
中科院分区：
文献类型：
--
作者：
Nadeau, S;Hein, P;Miller, FD
神经元损伤后诱导基因表达的分子机制还不清楚。在这里，我们解决这个问题，集中在C/EBP β一个转录因子参与细胞损伤和再生。我们发现，C/EBP β mRNA在整个成熟大脑的神经元中表达，并且轴突损伤后面部运动神经元中C/EBP β mRNA和磷蛋白的水平增加。为了确定这些增加的重要性，我们研究了再生相关的Tal α-微管蛋白基因，其启动子中含有功能性C/EBP结合位点。在转基因小鼠中，最小176个核苷酸的Tot] α-微管蛋白启动子：nlacZ报告基因的表达在受损的面部运动神经元中上调。这种损伤诱导的转录增加在C/EBP β-/-小鼠中受到抑制。在携带较大的1.1 kb启动子Totl：nlacZ报告基因构建体的C/EBP β-/-小鼠中观察到类似的抑制。此外，原位杂交显示，损伤诱导的表达上调的同源小鼠α 1 α-微管蛋白的mRNA，和第二个再生相关的mRNA，GAP-43，在C/FBP 13-/-小鼠受到抑制。因此，C/EBP β是神经元损伤反应所必需的，其作用是转录激活再生相关基因表达。(c)2005年爱思唯尔公司All rights reserved.
The molecular mechanisms responsible for inducing gene expression following neuronal injury are not well understood. Here, we address this issue by focusing upon C/EBP beta a transcription factor implicated in cellular injury and regeneration. We show that C/EBP beta mRNA is expressed in neurons throughout the mature brain and that levels of both C/EBP beta mRNA and phosphoprotein are increased in facial motor neurons following axonal injury. To determine the importance of these increases, we examined the regeneration-associated Tal alpha-tubulin gene which contains functional C/EBP binding sites in its promoter. In transgenic mice, expression of a minimal 176 nucleotide Tot] alpha-tubulin promoter:nlacZ reporter gene was upregulated in injured facial motor neurons. This injury-induced transcriptional increase was inhibited in C/EBP beta -/- mice. A similar inhibition was observed in C/EBP beta -/- mice that carried a larger 1.1-kb promoter Totl:nlacZ reporter construct. Moreover, in situ hybridization revealed that the injury-induced upregulation of the enclogenous mouse alpha 1 alpha-tubulin mRNA, and of a second regeneration-associated mRNA, GAP-43, was inhibited in C/FBP13 -/- mice. Thus, C/EBP beta is essential for the neuronal injury response, acting to transcriptionally activate regeneration-associated gene expression. (c) 2005 Elsevier Inc. All rights reserved.