<i>S100A2</i> Silencing Relieves Epithelial–Mesenchymal Transition in Pulmonary Fibrosis by Inhibiting the Wnt/β-Catenin Signaling Pathway

Abstract

Pulmonary fibrosis (PF) is a progressive and lethal disease with poor prognosis. <i>S100A2</i> plays an important role in the progression of cancer. However, the role of <i>S100A2</i> in PF has not yet been reported. In this study, we explored the potential role of <i>S100A2</i> in PF and its potential molecular mechanisms. Increased expression of <i>S100A2</i> was first observed in lung tissues of PF patients. We found that downregulation of <i>S100A2</i> inhibited the transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in A549 cells. Mechanically, TGF-β1 upregulated β-catenin and the phosphorylation of glycogen synthase kinase-3β, which was blocked by silencing <i>S100A2 in vitro</i>. Furthermore, lithium chloride (activator of the Wnt/β-catenin signaling pathway) effectively rescued <i>S100A2</i> knockdown-mediated inhibition of EMT in PF. In conclusion, these findings demonstrate that downregulation of <i>S100A2</i> alleviated PF through inhibiting EMT. <i>S100A2</i> is a promising potential target for further understanding the mechanism and developing a strategy for the treatment of PF and other EMT-associated diseases.