XAV-939 inhibits epithelial-mesenchymal transformation in pulmonary fibrosis induced by crystalline silica via the Wnt signaling pathway

Environ Toxicol. 2023 Feb;38(2):460-471. doi: 10.1002/tox.23693. Epub 2022 Oct 28.

Abstract

Silicosis is an occupational lung disease that results from long-term inhalation of free silica dust, the expression is sustained inflammation response, fibroblast hyperplasia, and excessive collagen deposit, bringing about pulmonary interstitial fibrosis. Wnt signaling pathway exists in various kinds of eukaryotic cells, is a highly conservative signaling pathway in biological evolution, and participates in cell proliferation, differentiation, migration, and polarity of physiological activity, such as in embryonic development, organ morphology, and tumor. In addition, it plays an important role in the progress of fibrosis disease. At present, studies related to silicosis are increasing, but the pathogenesis of silicosis still is not clear. In recent years, more and more studies have suggested that the Wnt signaling pathway could participate in the pathogenesis of silicosis fibrosis. In the study, we explored the mechanism of the Wnt signaling pathway in the pathogenesis of silicosis fibrosis and evaluated the effect of XAV-939 treatment epithelial-mesenchymal transformation (EMT) induced by silica. In addition, the results showed that EMT and activation of the Wnt signaling pathway would occur after stimulation of silica or TGF-β1. However, after treatment with the Wnt signaling pathway inhibitor XAV-939, EMT was reversed and the expression of the β-catenin decreased. These results suggested that the Wnt signaling pathway is associated with EMT induced by silica and it could be a potential target for the treatment of silicosis.

Keywords: Wnt signaling pathway; epithelial-mesenchymal transformation; silicosis.

MeSH terms

  • Epithelial-Mesenchymal Transition* / drug effects
  • Fibrosis
  • Humans
  • Pulmonary Fibrosis* / chemically induced
  • Silicon Dioxide / toxicity
  • Silicosis* / metabolism
  • Wnt Signaling Pathway / drug effects

Substances

  • Silicon Dioxide
  • XAV939