Pluripotent stem cells are have therapeutic applications in regenerative medicine and drug discovery. However, the differentiation of stem cells in vitro hinders their large-scale production and clinical applications. The maintenance of cell pluripotency relies on a complex network of transcription factors; of these, octamer-binding transcription factor-4 (Oct4) plays a key role. This study aimed to construct an Oct4 gene promoter-driven firefly luciferase reporter and screen small-molecule compounds could maintain cell self-renewal and pluripotency. The results showed that ethyl-p-methoxycinnamate (EPMC) enhance the promoter activity of the Oct4 gene, increased the expression of Oct4 at both mRNA and protein levels, and significantly promoted the colony formation of P19 cells. These findings suggesting that EPMC could reinforce the self-renewal capacity of P19 cells. The pluripotency markers Oct4, SRY-related high-mobility-group-box protein-2, and Nanog were expressed at higher levels in EPMC-induced colonies. EPMC could promote teratoma formation and differentiation potential of P19 cells in vivo. It also enhanced self-renewal and pluripotency of human umbilical cord mesenchymal stem cells and mouse embryonic stem cells. Moreover, it significantly activated the nuclear factor kappa B (NF-κB) signaling pathway via the myeloid differentiation factor 88-dependent pathway. The expression level of Oct4 decreased after blocking the NF-κB signaling pathway, suggesting that EPMC promoted the expression of Oct4 partially through the NF-κB signaling pathway. This study indicated that EPMC could maintain self-renewal and pluripotency of stem cells.

中文翻译：

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对甲氧基肉桂酸乙酯通过NF-κB信号通路增强oct4表达并增强多能性。

多能干细胞在再生医学和药物发现中具有治疗应用。然而，干细胞的体外分化阻碍了它们的大规模生产和临床应用。细胞多能性的维持依赖于转录因子的复杂网络。其中，八聚物结合转录因子4（Oct4）起着关键作用。这项研究旨在构建一个Oct4基因启动子驱动的萤火虫荧光素酶报道基因，并筛选能够维持细胞自我更新和多能性的小分子化合物。结果表明，对甲氧基肉桂酸乙酯（EPMC）增强了Oct4基因的启动子活性，增加了mRNA和蛋白质水平上Oct4的表达，并显着促进了P19细胞的集落形成。这些发现提示EPMC可以增强P19细胞的自我更新能力。多能性标志物Oct4，SRY相关的高迁移率族蛋白2和Nanog在EPMC诱导的菌落中以较高的水平表达。EPMC可以在体内促进畸胎瘤的形成和P19细胞的分化潜能。它还增强了人脐带间充质干细胞和小鼠胚胎干细胞的自我更新和多能性。此外，它通过髓样分化因子88依赖性途径显着激活了核因子κB（NF-κB）信号传导途径。阻断NF-κB信号通路后，Oct4的表达水平降低，提示EPMC部分通过NF-κB信号通路促进了Oct4的表达。