ZC3H4 Governs Epithelial Cell Migration through ROCK/p-PYK2/p-MLC2 Pathway in Silica-induced Pulmonary Fibrosis

  • Environ Toxicol Pharmacol. 2023 Oct 20:104301. doi: 10.1016/j.etap.2023.104301.
Rong Jiang  1 ,  Yichao Zhou  2 ,  Qianqian Gao  3 ,  Lei Han  4 ,  Zhen Hong  5
Affiliations
  • 1. Jiangsu Health Vocational College, Nanjing, Jiangsu Province, China.
  • 2. Department of Occupation Disease Prevention and Cure, Changzhou Wujin District Center for Disease Control and Prevention, Changzhou, Jiangsu Province, China. Electronic address: [email protected].
  • 3. Department of Occupation Disease Prevention and Cure, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China; Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • 4. Department of Occupation Disease Prevention and Cure, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China.
  • 5. Jiangsu Health Vocational College, Nanjing, Jiangsu Province, China. Electronic address: [email protected].
PMID: 37866415 DOI: 10.1016/j.etap.2023.104301
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/6J 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.

Keywords
Epithelial Cell Migration; ROCK/p-PYK2/p-MLC2; Silicosis; ZC3H4.
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