The epithelial–mesenchymal transition (EMT) process is a key priming activity of fibroblasts in pulmonary fibrosis during silicosis. Ets-like protein-1 (Elk-1) is a critical modulator that promotes functional changes in cells, and the effects are mediated by oxidative stress (OS). However, whether ELK-1 is involved in EMT of silicosis remains unclear. In addition, researchers have found that Elk-1 is involved in the expression of the gene zc3h12a, which encodes the protein MCPIP1, and MCPIP1 is a member of the zinc finger Cys-Cys-Cys-His (CCCH)-type protein family. A previous study from our lab showed that ZC3H4, which is also a member of the CCCH-type protein family, critically affected the regulation of EMT during silicosis. However, it has not yet been elucidated if ELK-1 acts at the promoter for zc3h4 to increase its expression in a mechanism that is similar to that of the zc3h12a gene and whether such regulation ultimately controls EMT. Therefore, we explored the correlation between ELK-1 and ZC3H4 expression and tested the underlying mechanisms affecting ELK-1 activation induced by silica. Our study identifies that SiO₂-mediated EMT via ELK-1, with the upstream activity of OS and the downstream signaling of ZC3H4 expression resulting in enhanced EMT. These findings suggest that the nuclear transcription factor ELK-1 may be useful as a novel target for the treatment of pulmonary fibrosis.

上皮-间质转化 (EMT) 过程是硅肺病期间肺纤维化中成纤维细胞的关键启动活动。Ets 样蛋白 1 (Elk-1) 是促进细胞功能变化的关键调节剂，其作用由氧化应激 (OS) 介导。然而，ELK-1 是否参与矽肺的 EMT 仍不清楚。此外，研究人员还发现Elk-1参与了编码MCPIP1蛋白的基因zc3h12a的表达，MC​​PIP1是锌指Cys-Cys-Cys-His (CCCH)型蛋白家族的成员。我们实验室之前的一项研究表明，ZC3H4 也是 CCCH 型蛋白家族的成员，严重影响矽肺病期间 EMT 的调节。但是，ELK-1是否起到启动子的作用尚未阐明zc3h4以类似于zc3h12a基因的机制增加其表达，以及这种调节是否最终控制 EMT。因此，我们探讨了 ELK-1 和 ZC3H4 表达之间的相关性，并测试了影响二氧化硅诱导的 ELK-1 激活的潜在机制。我们的研究确定了 SiO ₂通过 ELK-1 介导的 EMT，OS 的上游活性和 ZC3H4 表达的下游信号导致增强的 EMT。这些发现表明，核转录因子 ELK-1 可用作治疗肺纤维化的新靶点。