ZC3H4 governs epithelial cell migration through ROCK/p-PYK2/p-MLC2 pathway in silica-induced pulmonary fibrosis.

ABSTRACT

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 (SiO2)-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: 1) SiO2 upregulated epithelial migration in pulmonary fibrotic lesions. 2) ZC3H4 modulated SiO2-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.