Fibrinogen αC-Domain Derived From Group 1 Allergen of Dermatophagoides microceras Modulates Cell Adhesion in Human...

House dust mites (HDMs) allergens are major contributors to allergic asthma, with their protease activity playing a critical role in airway inflammation. Der m 1, a Group 1 HDMs allergen from Dermatophagoides microceras, is a cysteine protease known for its ability to degrade host proteins. In this study, we identified novel fibrinogen cleavage sites targeted by Der m 1, which are distinct from those cleaved by thrombin or plasmin. By employing biochemical and bioinformatic approaches, we identified the fibrinogen αC domain as a key component of Der m 1-derived fibrinogen cleavage products (FCPs). To assess their functional effects, we treated human bronchial epithelial cells with Der m 1-derived FCPs and the fibrinogen αC domain. Both treatments significantly enhanced cell adhesion, with effects peaking at 2-4 h post-treatment before gradually declining. Transcriptomic analysis, including RNA sequencing and gene set enrichment analysis (GSEA), revealed that both Der m 1-derived FCPs and the αC domain induced similar transcriptional responses, particularly in adhesion-related pathways involving integrin signaling. Functional validation using Cilengitide, a cyclic RGD peptide that antagonizes αVβ₃ and αVβ₅ integrins, confirmed that the pro-adhesive effects were integrin αV-dependent. These findings reveal that Der m 1 not only cleaves fibrinogen but also produces bioactive fragments that influence epithelial adhesion and signaling, offering new insight into airway remodeling in allergic asthma.