Epithelial-mesenchymal transition (EMT) induced by transforming growth factor-β1 (TGF-β1) is thought to be involved in the pathogenesis of pulmonary fibrosis. Emerging evidence suggested that there are some common causes between ferroptosis and pulmonary fibrosis. The interaction of EMT and ferroptosis and its mechanism were investigated by detecting the expression levels of α-smooth muscle actin (α-SMA), E-cadherin, solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) and measuring the contents of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH). The cellular morphology and ultrastructure of mitochondria were studied by microscope and transmission electron microscope (TEM), respectively. The results showed that ferroptosis in A549 cells was induced by Erastin, which decreased the expression levels of E-cadherin (E-Ca), α-SMA, and SLC7A11, accompanied with ROS and MDA increase, as well as GSH decrease. TGF-β1 promoted ultrastructure variation of mitochondria similar to ferroptosis and mesenchymal changes in morphology during EMT of A549 cells, accompanied with reduced GSH content and expression of SLC7A11, as well as ROS and MDA increase. Ferrostatin-1 (Fer-1) recovered ferroptosis induced by Erastin, but had no effect on the morphological change caused by TGF-β1. Furthermore, Fer-1 reduced ROS and MDA production, and increased SLC7A11 expression in the early subsequently increased GSH. However, the effects of Fer-1 on above indicators were different in time. The expression of GPX4 had no significant change during EMT induced by TGF-β1 and ferroptosis induced by Erastin in A549 cells. It is indicating that Erastin promoted the de-epithelialization of lung epithelial cells, but inhibited the process of myofibroblast differentiation; Fer-1 could partially inhibit EMT induced by TGF-β1, but reverse ferroptosis induced by Erastin. TGF-β1 could delay the ferroptosis, but could not prevent it. Lipid peroxidation, GSH depletion, and SLC7A11 inhibition are common causes of EMT and ferroptosis in A549 cells, but different in specific mechanisms. The exact effects of GPX4 involved in EMT and ferroptosis in A549 cells need further study.

中文翻译：

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脂质过氧化，谷胱甘肽耗竭和SLC7A11抑制是A549细胞EMT和肥大症的常见原因，但在具体机制上不同

转化生长因子-β1（TGF-β1）诱导的上皮-间质转化（EMT）被认为与肺纤维化的发病机制有关。越来越多的证据表明，肥大症和肺纤维化之间有一些共同的原因。通过检测α-平滑肌肌动蛋白（α-SMA），E-钙粘着蛋白，溶质载体家族7成员11（SLC7A11）和谷胱甘肽过氧化物酶4（GPX4）的表达水平来研究EMT与肥大症的相互作用及其机制。）并测量活性氧（ROS），丙二醛（MDA）和谷胱甘肽（GSH）的含量。线粒体的细胞形态和超微结构分别用显微镜和透射电镜（TEM）研究。结果表明，Elastin诱导了A549细胞的肥大化，从而降低了E-钙黏着蛋白（E- Caherin），α-SMA和SLC7A11的表达水平，并伴随着ROS和MDA的升高，以及GSH的降低。TGF-β1促进线粒体超微结构变化，类似于肥大症和A549细胞EMT期间的间质形态改变，同时GSH含量降低和SLC7A11表达以及ROS和MDA增加。Ferrostatin-1（Fer-1）恢复了Erastin引起的肥大作用，但对TGF-β1引起的形态变化没有影响。此外，Fer-1降低了ROS和MDA的产生，并在早期的GSH升高中增加了SLC7A11表达。但是，Fer-1对上述指标的影响在时间上是不同的。GPX4的表达TGF-β1诱导的EMT和Erastin诱导的A549细胞肥大作用没有明显变化。提示Elastin促进了肺上皮细胞的去上皮化，但抑制了肌成纤维细胞的分化。Fer-1可以部分抑制TGF-β1诱导的EMT，但可以逆转Erastin诱导的肥大作用。TGF-β1可以延缓肥大症，但不能阻止它。脂质过氧化，GSH耗竭和SLC7A11抑制是A549细胞EMT和肥大症的常见原因，但在特定机制上有所不同。GPX4参与A549细胞EMT和肥大症的确切作用有待进一步研究。