S100A2 Silencing Relieves Epithelial-Mesenchymal Transition in Pulmonary Fibrosis by Inhibiting the Wnt/beta-Catenin Signaling Pathway

摘要

Pulmonary fibrosis (PF) is a progressive and lethal disease with poor prognosis. S100A2 plays an important role in the progression of cancer. However, the role of S100A2 in PF has not yet been reported. In this study, we explored the potential role of S100A2 in PF and its potential molecular mechanisms. Increased expression of S100A2 was first observed in lung tissues of PF patients. We found that downregulation of S100A2 inhibited the transforming growth factor-beta 1 (TGF-beta 1)-induced epithelial-mesenchymal transition (EMT) in A549 cells. Mechanically, TGF-beta 1 upregulated beta-catenin and the phosphorylation of glycogen synthase kinase-3 beta, which was blocked by silencing S100A2 in vitro. Furthermore, lithium chloride (activator of the Wnt/beta-catenin signaling pathway) effectively rescued S100A2 knockdown-mediated inhibition of EMT in PF. In conclusion, these findings demonstrate that downregulation of S100A2 alleviated PF through inhibiting EMT. S100A2 is a promising potential target for further understanding the mechanism and developing a strategy for the treatment of PF and other EMT-associated diseases.