HSF1 is required for extra-embryonic development, postnatal growth and protection during inflammatory responses in mice
HSF1 is required for extra-embryonic development, postnatal growth and protection during inflammatory responses in mice
复制标题
DOI：
10.1093/emboj/18.21.5943
复制
发表时间：
1999-11-01
期刊：
影响因子：
11.4
通讯作者：
Benjamin, IJ
中科院分区：
文献类型：
--
作者：
Xiao, XZ;Zuo, XX;Benjamin, IJ
HSF 1是主要的热休克转录因子，其结合热休克蛋白（Hsps）启动子中的热休克元件（HSE）并控制受到各种环境胁迫的细胞中的快速Hsp诱导。尽管脊椎动物HSF家族的至少四个成员已经被描述，但是它们各自的生理作用的细节仍然相对模糊。我们创造了Hsf 1（-/-）缺陷小鼠，我们证明纯合Hsf 1（-/-）小鼠可以存活到成年，但表现出多种表型，包括：绒毛尿囊胎盘缺陷和产前致死性;生长迟缓;雌性不育;消除“经典”热休克反应;和过度的肿瘤坏死因子α产生导致内毒素攻击后死亡率增加，由于基础热休克蛋白的表达没有明显改变的HSF 1无效突变，我们的研究结果表明，这个因素，如果蝇HSF蛋白，可能参与调节其他重要的基因或信号通路。我们的研究结果建立了HSF 1反式激活因子在胚胎外发育过程中调节关键生理事件和在病理条件下（如脓毒症）调节促炎反应的直接因果效应，表明这些途径作为人类治疗靶点具有临床重要性。
HSF1 is the major heat shock transcriptional factor that binds heat shock element (HSE) in the promoter of heat shock proteins (Hsps) and controls rapid Hsp induction in cells subjected to various environmental stresses, Although at least four members of the vertebrate HSF family have been described, details of their individual physiological roles remain relatively obscure, To assess whether HSF1 exhibited redundant or unique in vivo functions, we created Hsf1(-/-) deficient mice, We demonstrate that homozygous Hsf1(-/-) mice can survive to adulthood but exhibit multiple phenotypes including: defects of the chorioallantoic placenta and prenatal lethality; growth retardation; female infertility; elimination of the 'classical' heat shock response; and exaggerated tumor necrosis factor alpha production resulting in increased mortality after endotoxin challenge, Because basal Hsp expression is not altered appreciably by the HSF1 null mutation, our findings suggest that this factor, like Drosophila Hsf protein, might be involved in regulating other important genes or signaling pathways. Our results establish direct causal effects for the HSF1 transactivator in regulating critical physiological events during extraembryonic development and under pathological conditions such as sepsis to modulate pro-inflammatory responses, indicating that these pathways have clinical importance as therapeutic targets in humans.