Airway epithelial overexpressed CTSK induces airway remodeling through EMTU activation in asthma

Accumulating studies in recent years have revealed that airway remodeling is involved in the occurrence, development, and treatment sensitivity of asthma. Airway epithelial cells (AECs) regulate the activation of epithelial-mesenchymal trophic units (EMTUs) during airway remodeling through secretion of a series of signaling mediators. However, the major trigger and the intrinsic pathogenesis of airway remodeling is still obscure. Here, we show that the expression of CTSK in airway epithelia increased significantly along with the development of airway remodeling in HDM-stressed asthma model. Increased secretion of CTSK from airway epithelia induced the activation of EMTU through the activation of PAR2-mediated pathway. We found that CTSK is a potential biomarker of airway remodeling for asthma patients that can reflect the degree of airway remodeling and the severity of asthma. Blockade of CTSK inhibits EMTU activation and alleviate airway remodeling effectively that is an effective intervention target of airway remodeling. Thus, our findings provide that CTSK is a potential biomarker for airway remodeling which may also be a useful target for the targeted intervention of airway remodeling in asthma patients.