AP-1 and the injury response of the GFAP gene.
AP-1 and the injury response of the GFAP gene.
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DOI：
10.1002/jnr.24338
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发表时间：
2019-03
影响因子：
4.2
通讯作者：
Olsen ML
中科院分区：
文献类型：
--
作者：
Brenner M;Messing A;Olsen ML
增加的GFAP基因表达是CNS损伤的共同特征，导致其用作研究产生神经胶质增生的机制的报告基因。AP-1转录因子被认为参与介导反应性应答。先前的研究发现GFAP启动子中的共有AP-1结合位点对于转染到培养细胞中的报告构建体的活性是必需的，但对小鼠中的基础转基因表达几乎没有影响。由于培养的星形胶质细胞显示出反应性星形胶质细胞的一些特性，这些发现表明AP-1转录因子对于损伤中GFAP的上调是至关重要的，但对于其静息表达水平不是至关重要的。我们通过比较由含有野生型AP-1结合位点的人GFAP启动子驱动的lacZ转基因小鼠中的损伤反应与该位点突变的小鼠中的损伤反应来研究这种可能性。发现完整的AP-1位点对于GFAP启动子对所使用的三种不同损伤模型的反应至关重要：由冷冻损伤产生的物理创伤、由红藻氨酸产生的癫痫发作和在亚历山大疾病模型中产生的慢性神经胶质增生。另一个意想不到的发现是，野生型启动子驱动的lacZ转基因的应答基本上低于内源性小鼠GFAP基因的应答。这表明GFAP基因具有先前未识别的损伤响应元件，其位于转录起始位点的上游，而不是本文所用的GFAP启动子片段中存在的2.2kb。
Increased GFAP gene expression is a common feature of CNS injury, resulting in its use as a reporter to investigate mechanisms producing gliosis. AP-1 transcription factors are among those proposed to participate in mediating the reactive response. Prior studies found a consensus AP-1 binding site in the GFAP promoter to be essential for activity of reporter constructs transfected into cultured cells, but to have little to no effect on basal transgene expression in mice. Since cultured astrocytes display some properties of reactive astrocytes, these findings suggested that AP-1 transcription factors are critical for the upregulation of GFAP in injury, but not for its resting level of expression. We have examined this possibility by comparing the injury response in mice of lacZ transgenes driven by human GFAP promoters that contain the wild type AP-1 binding site to those in which the site is mutated. An intact AP-1 site was found critical for a GFAP promoter response to the three different injury models used: physical trauma produced by cryoinjury, seizures produced by kainic acid, and chronic gliosis produced in an Alexander disease model. An unexpected additional finding was that the responses of the lacZ transgenes driven by the wild type promoters were substantially less than that of the endogenous mouse GFAP gene. This suggests that the GFAP gene has previously unrecognized injury-responsive elements that reside further upstream of the transcription start site than the 2.2 kb present in the GFAP promoter segments used here.
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影响因子：
5.3
作者：
Ben Haim L;Carrillo-de Sauvage MA;Ceyzériat K;Escartin C
通讯作者：
Escartin C
影响因子：
5.3
作者：
Cole-Edwards, Kasie K.;Musto, Alberto E.;Bazan, Nicolas G.
通讯作者：
Bazan, Nicolas G.
影响因子：
6.2
作者：
JOHNSON, WB;RUPPE, MD;MUCKE, L
通讯作者：
MUCKE, L
影响因子：
6.2
作者：
Lee, Y;Su, M;Brenner, M
通讯作者：
Brenner, M
DOI：
10.1016/0169-328x(90)90078-r
发表时间：
1990-05-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
BRENNER, M;LAMPEL, K;FREESE, E
通讯作者：
FREESE, E