Stressor and Glucocorticoid-Dependent Induction of the Immediate Early Gene Kruppel-Like Factor 9: Implications for Neural Development and Plasticity
Stressor and Glucocorticoid-Dependent Induction of the Immediate Early Gene Kruppel-Like Factor 9: Implications for Neural Development and Plasticity
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DOI：
10.1210/en.2008-1441
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发表时间：
2009-04-01
期刊：
影响因子：
4.8
通讯作者：
Denver, Robert J.
中科院分区：
文献类型：
--
作者：
Bonett, Ronald M.;Hu, Fang;Denver, Robert J.
Kruppel样因子9（KLF 9）是一种由甲状腺激素诱导的，与脊椎动物神经发育有关的立即早期基因。我们分析了应激和糖皮质激素（GC）依赖调节KLF 9表达的青蛙非洲爪蟾的大脑，并调查了可能的作用KLF 9在神经元分化。暴露于震动/限制应激增加血浆皮质酮（CORT）浓度，和KLF 9免疫反应在几个脑区，其中包括内侧杏仁核和床核的终纹，前视前区（同源的哺乳动物室旁核），和视顶盖（同源的哺乳动物上级丘）。预先用GC受体拮抗剂RU 486阻断应激诱导的KLF 9 mRNA表达，或注射CORT模拟应激诱导的KLF 9 mRNA表达。CORT处理后，X细胞KLF 9 mRNA表达迅速增加，并呈剂量依赖性。Iaevis XTC-2细胞，其对蛋白质合成的抑制具有抗性。RU 486可阻断CORT对XTC-2细胞KLF 9表达的作用，但盐皮质激素受体拮抗剂螺内酯不能阻断CORT对KLF 9表达的作用。为了测试KLF 9上调的功能后果，我们通过电穿孔介导的基因转移将KLF 9表达质粒引入活体蝌蚪脑中。KLF 9在蝌蚪脑中的强制表达引起Golgi染色细胞的增加，反映神经元分化/成熟。我们的研究结果支持KLF 9是一个直接的，GC受体的靶基因，是由压力诱导，并作为一个中介的行动GC对大脑基因表达和神经元结构的功能。（内分泌学150：1757-1765，2009）
Kruppel-like factor 9 (KLF9) is a thyroid hormone-induced, immediate early gene implicated in neural development in vertebrates. We analyzed stressor and glucocorticoid (GC)-dependent regulation of KLF9 expression in the brain of the frog Xenopus laevis, and investigated a possible role for KLF9 in neuronal differentiation. Exposure to shaking/confinement stressor increased plasma corticosterone (CORT) concentration, and KLF9 immunoreactivity in several brain regions, which included the medial amygdala and bed nucleus of the stria terminalis, anterior preoptic area (homologous to the mammalian paraventricular nucleus), and optic tectum (homologous to the mammalian superior colliculus). The stressor-induced KLF9 mRNA expression in the brain was blocked by pretreatment with the GC receptor antagonist RU486, or mimicked by injection of CORT. Treatment with CORT also caused a rapid and dose-dependent increase in KLF9 mRNA in X. laevis XTC-2 cells that was resistant to inhibition of protein synthesis. The action of CORT on KLF9 expression in XTC-2 cells was blocked by RU486, but not by the mineralocorticoid receptor antagonist spironolactone. To test for functional consequences of up-regulation of KLF9, we introduced a KLF9 expression plasmid into living tadpole brain by electroporation-mediated gene transfer. Forced expression of KLF9 in tadpole brain caused an increase in Golgi-stained cells, reflective of neuronal differentiation/maturation. Our results support that KLF9 is a direct, GC receptor target gene that is induced by stress, and functions as an intermediary in the actions of GCs on brain gene expression and neuronal structure. (Endocrinology 150: 1757-1765, 2009)