Spon2 knockdown suppresses the phenotype of house dust mite-induced allergic asthma in mice and cells.

Abstract

Allergic asthma is a chronic inflammatory disease of the airways. The objective of this study was to identify potential therapeutic targets for allergic asthma through RNA sequencing (RNA-seq) and experimental analyses. Allergic asthma models, both in cells and mice, were induced using house dust mite (HDM) treatment. RNA-seq analysis of lung tissues from HDM-induced allergic asthma mice and control mice was performed to identify differentially expressed genes (DEGs), and functional enrichment analysis of DEGs was performed. Spon2 knockdown was achieved via siRNA transfection and adeno-associated virus transduction. Bronchoalveolar lavage fluid (BALF) from mice was analyzed using cytology, ELISA for cytokines, and Giemsa staining. Lung tissues underwent HE staining, immunohistochemical staining, and Masson staining. Key gene expression levels were monitored in cellular and mouse models using real-time quantitative PCR and western blotting. RNA-seq and histological analysis of the HDM-induced allergic asthma mouse model revealed increased macrophage infiltration and upregulation of Spon2 in the lung tissues of mice with allergic asthma. Compared with the HDM-induced group, Spon2 knockdown led to decreased levels of inflammatory cytokines in the cellular model and, in the mouse model, it relieved HDM-caused histopathological alterations in mouse lungs, reduced collagen fiber deposition, lowered HDM-specific IgE expression in serum, and mitigated the HDM-induced increase in CD80 expression in lung tissues, total cell counts, and cytokine levels (IL-13, TNF-α, IFN-γ, IL-4, IL-5, IL-10) in BALF. Spon2 plays a role in the progression of HDM-induced allergic asthma and may be a potential therapeutic target worthy of further in vivo investigation.