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.

Background: Asthma is a complex pulmonary inflammatory disease which is common among older adults.Aging-related alterations have also been found in structural cells and immune cells of asthma patients. Of note, DNA methylation have been proven to be play a critical mechanism for age-related gene expression changes However, the methylation changes of aging-related genes in asthma patients is still obscure. Methods: First, changes in DNAm and gene expression were detected with multiple targeted bisulfite enrichment sequencing and qPCR in peripheral blood of 51 healthy controls and 55 asthmatic patients. Secondly, the correlation between the DNAm levels of specific altered CpG sites and the pulmonary function indicators of asthma patients was evaluated. Lastly, ROC curve and PCA were used to identify the feasibility of the candidate CpG sites as biomarkers for asthma. Results: Compared with HCs, there was a differential mRNA expression for 9 aging-related gene in peripheral blood of asthma patients. Besides, the methylation level of the 9 aging-related genes were also altered, and a total of 68 CpG sites were associated with the severity of asthma. Moreover, ROC curve and PCA analysis showed that the candidate differential methylation sites can be used as potential biomarkers for asthma. Conclusions: In summary, this study confirmed the differentially expressed mRNA and aberrant DNAm level of aging-related genes in asthma patients. The differential DMSs are associated with the clinical evaluation indicators of asthma, which indicate the involvement of aging-related genes in the pathogenesis of asthma and provide some new possible biomarker for asthma.