Activating transcription factor 4 (Atf4), which is modulated by the protein kinase RNA-like ER kinase (PERK), is a stress-induced transcription factor responsible for controlling the expression of a wide range of adaptive genes, enabling cells to withstand stressful conditions. However, the impact of the Atf4 signaling pathway on airway regeneration remains poorly understood. In this study, we used mouse airway epithelial cell culture models to investigate the role of PERK/Atf4 in respiratory tract differentiation. Through pharmacological inhibition and silencing of ATF4, we uncovered the crucial involvement of PERK/Atf4 in the differentiation of basal stem cells, leading to a reduction in the number of secretory cells. ChIP-seq analysis revealed direct binding of ATF4 to regulatory elements of genes associated with osteoblast differentiation and secretory cell function. Our findings provide valuable insights into the role of ATF4 in airway epithelial differentiation and its potential involvement in innate immune responses and cellular adaptation to stress.

中文翻译：

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早期 Atf4 活性驱动气道俱乐部和杯状细胞分化。

激活转录因子 4 (Atf4) 受蛋白激酶 RNA 样 ER 激酶 (PERK) 调节，是一种应激诱导的转录因子，负责控制多种适应性基因的表达，使细胞能够承受应激条件。然而，Atf4 信号通路对气道再生的影响仍知之甚少。在本研究中，我们使用小鼠气道上皮细胞培养模型来研究PERK/Atf4在呼吸道分化中的作用。通过药理学抑制和沉默 ATF4，我们发现 PERK/Atf4 在基底干细胞分化中的关键参与，导致分泌细胞数量减少。ChIP-seq 分析揭示 ATF4 与成骨细胞分化和分泌细胞功能相关基因的调控元件直接结合。我们的研究结果为了解 ATF4 在气道上皮分化中的作用及其在先天免疫反应和细胞对应激的适应中的潜在参与提供了有价值的见解。