Expression of S100A4 in Alveolar Epithelial Cells and Its Impact on Alveolar Epithelial Cell Function

Objective This study aimed to analyze the expression of S100A4 in alveolar epithelial cells and its impact on cellular function.Methods The single-cell dataset GSE213085 related to allergic asthma was downloaded from the Gene Expression Omnibus (GEO). Data visualization and analysis of S100A4 expression characteristics in alveolar epithelial cells were performed using R software. An ovalbumin (OVA)-induced asthmatic mouse model was established. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected. The expression levels of S100A4 were detected by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry. Human alveolar epithelial cells (A549) and mouse lung epithelial cells (MLE-12) were cultured *ex vivo* and stimulated with recombinant S100A4 protein. The expression changes of epithelial-mesenchymal transition (EMT)-related markers (E-cadherin, α-smooth muscle actin [α-SMA], and vimentin) were assessed by qRT-PCR and Western blot. Cell migration ability was evaluated using scratch wound healing and Transwell assays.Results Bioinformatic analysis revealed that S100A4 expression was significantly upregulated in alveolar type II epithelial cells (AT2 cells) from the asthmatic model. In the asthmatic mouse model, S100A4 expression in lung tissues was also markedly increased. Exogenous S100A4 treatment induced a morphological shift from an epithelial to a mesenchymal phenotype in lung epithelial cells, significantly enhanced cell migration, and was accompanied by downregulation of the epithelial marker E-cadherin and upregulation of the mesenchymal markers α-SMA and vimentin.Conclusion S100A4 expression is elevated in alveolar type II epithelial cells under asthmatic conditions. S100A4 can promote EMT in alveolar epithelial cells and may be one of the key factors driving airway remodeling in asthma. This finding provides a new perspective for understanding the progression of asthma and suggests a potential novel target for future therapeutic strategies.