Bioinformatics Analysis and Animal Experiments Revealed the Potential Role of IGFBP3 in Allergic Rhinitis.

Abstract

Background：Allergic rhinitis (AR) is a prevalent chronic inflammatory disorder that severely impairs patients' quality of life. Despite the availability of therapeutic interventions, the fundamental molecular mechanisms driving AR pathogenesis remain incompletely elucidated. Notably, the contribution of hypoxia-associated genes to nasal mucosal inflammation in AR has not been fully characterized. Methods：We conducted a comprehensive bioinformatics analysis on two public gene expression datasets-GSE261239 (human-derived) and GSE171005 (mouse-derived)-to identify hypoxia-related genes with differential expression in AR. A reference panel of hypoxia-associated genes was curated using the Molecular Signatures Database (MsigDB) and GeneCards. Immune cell infiltration patterns were evaluated via the xCell tool, and protein-protein interaction (PPI) networks were constructed using the STRING database. Subsequently, we validated these in silico findings in an ovalbumin (OVA)-induced mouse model of AR. Finally, we assessed the therapeutic potential of insulin-like growth factor-binding protein 3 (IGFBP3) by treating AR mice with recombinant IGFBP3. Results：Our analysis identified 11 hypoxia-related genes with altered expression in AR, among which IGFBP3 emerged as a central hub gene and was significantly downregulated. Reduced IGFBP3 expression was negatively correlated with the infiltration of mast cells (r=-0.43, p=0.037) and Th1 cells (r=-0.44, p=0.035). Consistent with the bioinformatics results, IGFBP3 expression was markedly decreased in the nasal tissues of AR mice. Treatment with recombinant IGFBP3 significantly alleviated allergic symptoms and reduced serum IgE levels (p=0.045) in AR mice. Furthermore, IGFBP3 treatment restored the integrity of the nasal epithelial barrier and diminished inflammatory cell accumulation in the nasal mucosa. Conclusion：Our findings demonstrate that IGFBP3 acts as a key regulator in AR pathogenesis, likely by modulating the local hypoxic microenvironment and regulating immune cell activity. The successful mitigation of AR symptoms following IGFBP3 treatment highlights its potential as a novel therapeutic target for AR.