The transcription factor Hhex regulates inflammation-related genes in microglia
The transcription factor Hhex regulates inflammation-related genes in microglia
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转录因子 Hhex 调节小胶质细胞中炎症相关基因
DOI：
10.1016/j.jphs.2022.04.006
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发表时间：
2022
影响因子：
3.5
通讯作者：
Furuyashiki Tomoyuki
中科院分区：
文献类型：
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作者：
Sakate Risa;Nishiyama Masahiro;Fukuda Yu;Kitaoka Shiho;Furuyashiki Tomoyuki
小胶质细胞具有多种生理和病理功能。然而，转录机制仍然难以捉摸。在这里，我们从应激小鼠的小胶质细胞转录组中寻找与小胶质细胞功能相关的新的转录因子，并评估它们在原代小胶质细胞中的作用。TLR2和TLR4激动剂增加原代小胶质细胞的REL、ATF3和CEBPB，降低HEX，作为反复的社会失败应激。虽然HHEX没有在小胶质细胞中进行研究，但TLR2和TLR4激动剂降低了HHEX，HHEX的过度表达减弱了TLR4增加的炎症相关基因的表达。这些发现表明，HHEX负性调节小胶质细胞中的炎症相关基因，TLR2/4激活降低HHEX，促进TLR4介导的神经炎症。
Microglia have diverse physiological and pathological functions. However, the transcriptional mechanisms remain elusive. Here we sought new transcription factors relevant to microglial functions from the microglial transcriptome of stressed mice and evaluated their roles in primary microglia. TLR2 and TLR4 agonists increased Rel, Atf3, and Cebpb and decreased Hhex in primary microglia as repeated social defeat stress. Although Hhex was not studied in microglia, TLR2 and TLR4 agonists decreased Hhex, and Hhex overexpression attenuated TLR4-increased expression of inflammation-related genes. These findings suggest that Hhex negatively regulates inflammation-related genes in microglia and that TLR2/4 activation reduces Hhex, facilitating TLR4-mediated neuroinflammation.