Fibrinogen αC-Domain derived from Group 1 Allergen of Dermatophagoides microceras modulates cell adhesion in human bronchial epithelial Cells

ABSTRACT: 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 hours post-treatment before gradually declining. Transcriptomic analysis, including RNA sequencing (RNA-seq) and gene set enrichment analysis (GSEA), revealed that both Der m 1-derived FCPs and the αC domain induced similar transcriptional responses, particularly in pathways related to cell adhesion, extracellular matrix organization, and integrin signaling. Notably, integrin αV (ITGAV) was identified as a central regulatory hub, suggesting that Der m 1-derived FCPs influence cell adhesion through integrin-mediated mechanisms. To explore this further, integrin-mediated adhesion was evaluated using Cilengitide, a cyclic RGD peptide that antagonizes αVβ3 and αVβ5 integrins. Co-treatment with Cilengitide significantly suppressed the pro-adhesive effects of both FCPs and αC domain, confirming an integrin αV-dependent mechanism. These findings reveal a novel interaction between the protease allergens of HDMs and host proteins. Specifically, they demonstrated that Der m 1 not only cleaves fibrinogen but also generates bioactive fragments that regulate epithelial cell adhesion and signaling. This study sheds new light on the role of HDMs allergen-derived proteases in airway remodeling and allergic asthma pathogenesis, highlighting potential therapeutic opportunities targeting Der m 1 proteolytic activity and its bioactive cleavage products.

ORGANISM(S): Homo sapiens

PROVIDER: GSE294310 | GEO | 2026/04/01

REPOSITORIES: GEO