Maintenance of olfactory neurogenesis requires HSF1, a major heat shock transcription factor in mice
Maintenance of olfactory neurogenesis requires HSF1, a major heat shock transcription factor in mice
复制标题
DOI：
10.1074/jbc.m506911200
复制
发表时间：
2006-02-24
影响因子：
4.8
通讯作者：
Nakai, A
中科院分区：
文献类型：
--
作者：
Takaki, E;Fujimoto, M;Nakai, A
热休克转录因子（HSFs）不仅参与热休克反应，而且参与生殖器官、脑和透镜的发育。在这里，我们分析了感觉器官，发现异常的嗅上皮在成年HSF 1基因敲除小鼠，这是发育相关的透镜。嗅觉上皮是正常的，直到出生后3周，但没有维持超过4周的HSF1基因敲除小鼠。嗅上皮萎缩，嗅感觉神经元死亡增加。上皮细胞的分析表明，诱导HSP表达和LIF表达的减少是缺乏在成年HSF1基因敲除小鼠。我们发现，DNA结合活性的HSF 1诱导在嗅上皮细胞后4周，HSF 1直接结合Lif基因，抑制其表达。HSF4对LIF表达和嗅觉神经发生具有相反的作用。这些数据表明，HSF1是必需的热休克蛋白和细胞因子基因的精确表达，这是强制性的维持成年小鼠的嗅觉神经发生，并表明，压力相关的过程参与其维护。
Heat shock transcription factors (HSFs) play roles not only in heat shock response but also in development of the reproductive organs, brain, and lens. Here, we analyzed sensory organs and found abnormalities of the olfactory epithelium in adult HSF1-null mice, which is developmentally related to the lens. The olfactory epithelium was normal until postnatal 3 weeks but was not maintained later than 4 weeks in HSF1-null mice. The olfactory epithelium was atrophied with increased cell death of olfactory sensory neurons. Analysis of the epithelium revealed that induction of HSP expression and reduction of LIF expression are lacking in adult HSF1-null mice. We found that DNA binding activity of HSF1 is induced in the olfactory epithelium later than 4 weeks and that HSF1 binds directly to Lif gene and inhibits its expression. HSF4 has opposing effects on LIF expression and olfactory neurogenesis. These data indicate that HSF1 is required for the precise expression of Hsp and cytokine genes that is obligatory for maintenance of olfactory neurogenesis in adult mice and suggest that stress-related processes are involved in its maintenance.