ZC3H4 通过 ROCK/p-PYK2/p-MLC2 通路调控二氧化硅诱导的肺纤维化中上皮细胞迁移。
ZC3H4 governs epithelial cell migration through ROCK/p-PYK2/p-MLC2 pathway in silica-induced pulmonary fibrosis.
机构信息
Jiangsu Health Vocational College, Nanjing, Jiangsu Province, China.
Department of Occupation Disease Prevention and Cure, Changzhou Wujin District Center for Disease Control and Prevention, Changzhou, Jiangsu Province, China.
出版信息
Environ Toxicol Pharmacol. 2023 Nov;104:104301. doi: 10.1016/j.etap.2023.104301. Epub 2023 Oct 21.
BACKGROUND
Increased epithelial migration capacity is a key step accompanying epithelial-mesenchymal transition (EMT). Our lab has described that ZC3H4 mediated EMT in silicosis. Here, we aimed to explore the mechanisms of ZC3H4 by which to stimulate epithelial cell migration.
METHODS
Silicon dioxide (SiO)-induced pulmonary fibrosis (PF) animal models were administered by intratracheal instillation in C57BL/6 J mice. Pathological analysis and 2D migration assay were established to uncover the pulmonary fibrotic lesions and epithelial cell migration, respectively. Inhibitors targeting ROCK/p-PYK2/p-MLC2 and CRISPR/Cas9 plasmids targeting ZC3H4 were administrated to explore the signaling pathways.
RESULTS
- SiO upregulated epithelial migration in pulmonary fibrotic lesions. 2) ZC3H4 modulated SiO-induced epithelial migration. 3) ZC3H4 governed epithelial migration through ROCK/p-PYK2/p-MLC2 signaling pathway.
CONCLUSIONS
ZC3H4 regulates epithelial migration through the ROCK/p-PYK2/p-MLC2 signaling pathway, providing the possibility that molecular drugs targeting ZC3H4-overexpression may exert effects on pulmonary fibrosis induced by silica.
背景
上皮细胞迁移能力的增加是伴随上皮-间充质转化（EMT）的关键步骤。我们的实验室已经描述了 ZC3H4 在矽肺中的 EMT 作用。在这里，我们旨在探讨 ZC3H4 刺激上皮细胞迁移的机制。
方法
通过气管内滴注二氧化硅（SiO）在 C57BL/6J 小鼠中建立肺纤维化（PF）动物模型。建立病理学分析和 2D 迁移实验，分别揭示肺纤维化病变和上皮细胞迁移。用靶向 ROCK/p-PYK2/p-MLC2 的抑制剂和靶向 ZC3H4 的 CRISPR/Cas9 质粒进行处理，以探讨信号通路。
结果
1）SiO 上调了肺纤维化病变中的上皮迁移。2）ZC3H4 调节了 SiO 诱导的上皮迁移。3）ZC3H4 通过 ROCK/p-PYK2/p-MLC2 信号通路调控上皮迁移。
结论
ZC3H4 通过 ROCK/p-PYK2/p-MLC2 信号通路调节上皮迁移，这为靶向 ZC3H4 过表达的分子药物可能对二氧化硅诱导的肺纤维化产生影响提供了可能性。
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