The transcription factor C/EBPβ promotes vascular endothelial growth factor A expression and neural stem cell expansion.

The transcription factor C/EBPβ promotes vascular endothelial growth factor A expression and neural stem cell expansion.
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转录因子C/EBPβ促进血管内皮生长因子A表达和神经干细胞扩增。

DOI:
10.1002/1873-3468.14405
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发表时间:
2022-07
期刊:
影响因子:
3.5
通讯作者:
Halterman MW
Halterman MW
中科院分区:
生物学3区
文献类型:
--
作者:
Li Y;Schor J;Bartko J;Albert G;Halterman MW

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bZIP转录因子CCAAT增强子结合蛋白β(C/EBPβ)在中枢神经系统中表现出神经原性、神经突原性和促生存作用。在这里,我们发现C/EBPβ通过作用于Vegf-a启动子内的C/EBPβ反应元件来调节神经干细胞(NSC)扩增和血管内皮生长因子A(VEGF-A)水平。正如预测的那样,C/EBPβ耗竭减少了增殖培养物中VEGF-A的产生、NSC数量和平均神经球大小。相反,C/EBPβ阻遏物CHOP-10的缺失诱导C/EBPβ和VEGF-A表达,同时刺激NSC扩增。这些数据强调了C/EBPβ在调节VEGF-A产生和NSC生长中的作用,并表明C/EBPβ的CHOP依赖性拮抗作用可能作为转录变阻器起作用,将应激相关线索与影响神经原性生态位的其他病理反应中的干细胞静止联系起来。CCAAT增强子结合蛋白β(C/EBPβ)作用于血管内皮生长因子A(Vegf-a)启动子内的顺式元件并增加VEGF-A表达。在增殖的神经干细胞(NSC)培养物中,C/EBPβ增强VEGF-A的产生和分泌,以及NSC数量和神经球大小。相反,C/EBP同源蛋白-10(CHOP-10)抑制C/EBPβ和VEGF-A表达,同时抑制NSC扩增。
The bZIP transcription factor CCAAT enhancer-binding protein β (C/EBPβ) exhibits neurogenic, neuritogenic, and pro-survival effects in the central nervous system. Here, we show that C/EBPβ regulates neural stem cell (NSC) expansion and vascular endothelial growth factor A (VEGF-A) level by acting on a C/EBPβ-responsive element within the Vegf-a promoter. As predicted, C/EBPβ depletion reduced VEGF-A production, NSC number, and average neurosphere size in proliferating cultures. Conversely, deletion of the C/EBPβ repressor CHOP-10 induced C/EBPβ and VEGF-A expression, while stimulating NSC expansion. These data highlight the role of C/EBPβ in regulating VEGF-A production and the growth of NSCs and suggest CHOP-dependent antagonism of C/EBPβ may function as a transcriptional rheostat linking stress-associated cues with stem cell quiescence among other pathological responses affecting the neurogenic niche. CCAAT enhancer-binding protein β (C/EBPβ) acts on cis elements within the vascular endothelial growth factor A (Vegf-a) promoter and increases VEGF-A expression. In proliferating neural stem cell (NSC) cultures, C/EBPβ enhances VEGF-A production and secretion, as well as NSC number and neurosphere size. Conversely, C/EBP homologous protein-10 (CHOP-10) inhibits C/EBPβ and VEGF-A expression, while suppressing NSC expansion.
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