GATA1 promotes TGF-β1-induced epithelial-mesenchymal transition by regulating GSDMB in human bronchial epithelial cells.

Asthma is a common inflammatory airway disorder characterized by recurrent cough, chest tightness, and dyspnea. The repeated inflammation of bronchial epithelial cells leading to epithelial-mesenchymal transition is believed to play a pivotal role in airway remodeling associated with asthma. Gasdermin B (GSDMB), a member of the gasdermin family of structurally related proteins, has been identified as having a strong association with asthma. However, the precise role of GSDMB in asthma pathophysiology remains ambiguous. This study aimed to elucidate the biological function of GSDMB in asthma and its upstream regulatory mechanisms. Our findings demonstrated that GSDMB expression was also increased in human bronchial epithelial cells stimulated with transforming growth factor-β1 (TGF-β1). Overexpression of GSDMB resulted in an upregulation of intermediate mesenchymal markers following TGF-β1 treatment, thereby facilitating epithelial-mesenchymal transition (EMT) processes. Furthermore, GSDMB enhanced both proliferation and migration capacity in TGF-β1-treated Beas-2B cells. Notably, the transcription factor GATA1 was found to bind to the promoter region of GSDMB and facilitate its expression levels. These results indicate that the transcriptional axis involving GATA1/GSDMB exerts functions promoting EMT along with enhancing cellular proliferation and migration within TGF-β1-stimulated bronchial epithelial cells; suggesting that targeting GSDMB may represent a viable therapeutic strategy for managing asthma.