High expression of ITGB3 ameliorates asthma by inhibiting epithelial-mesenchymal transformation through suppressing the activation of NF-kB pathway.

Integrin β3 (ITGB3) has been identified as an asthma-associated gene; however, its molecular mechanisms remain poorly understood. Epithelial-mesenchymal transition (EMT) is a critical driver of airway remodeling in asthma, which underpins disease progression. This study aimed to elucidate the role of ITGB3 in asthma pathogenesis by investigating its regulation of EMT. Asthma models were established in vivo using C57BL/6 mice and in vitro with A549 cells, both exposed to house dust mite (HDM) extract. The effects of HDM and ITGB3 modulation on cellular viability, apoptosis, and inflammatory cytokines (IL-4, IL-5, IL-13) were assessed in cultured cells and murine lungs. EMT was evaluated via western blot analysis of E-cadherin, N-cadherin, and vimentin expression. The NF-κB pathway was examined by quantifying phosphorylated p65 and IkBa levels. Lung tissue pathology and ITGB3 expression were assessed using hematoxylin and eosin (H&E) staining and immunohistochemistry. Results demonstrated that HDM exposure reduced A549 cell viability, increased cytotoxicity, apoptosis, and pro-inflammatory cytokine production, while promoting EMT. ITGB3 knockdown exacerbated these effects, whereas ITGB3 overexpression mitigated them. Furthermore, HDM activated the NF-κB pathway, an effect reversed by ITGB3 overexpression. In HDM-challenged cells, NF-κB activation via an agonist counteracted the protective effects of ITGB3 overexpression on apoptosis, inflammation, and EMT. Notably, ITGB3 overexpression suppressed inflammation, EMT, and pathological remodeling in asthmatic mice. Collectively, our findings reveal that ITGB3 exerts protective effects in asthma by inhibiting EMT through suppression of the NF-κB signaling pathway, thereby identifying ITGB3 as a potential therapeutic target for asthma management.