Revealing shared gene signatures and HIF-1α pathway in allergic rhinitis and asthma: a bioinformatics and experimental study

Background Allergic rhinitis (AR) and asthma (AS) are closely linked in both epidemiology and pathogenesis, though the mechanisms remain unclear. This study aims to identify shared gene signatures and molecular mechanisms in the combined allergic rhinitis and asthma syndrome (CARAS) and validate these findings in a murine model.Method Gene expression data from the GEO database (GSE52804 for AR, GSE6858, and GSE41665 for AS) were analyzed. Differentially expressed genes (DEGs) were identified through bioinformatics. A protein-protein interaction (PPI) network was constructed using STRING, and hub genes were determined via Cytoscape. Gene Ontology (GO) and KEGG pathway analyses were conducted. A murine CARAS model was used to validate the role of the HIF-1α pathway.Results We identified 56 DEGs, with IL6, Cxcl1, Ccl9, Cxcl2, Ccl20, Ccl11, and Cxcl5 as key hub genes. Key pathways influencing CARAS included viral protein interactions with cytokines, arachidonic acid metabolism, and HIF-1 signaling. CARAS mice exhibited substantial inflammation in nasal and lung tissues, accompanied by elevated levels of inflammatory cytokines and increased expression of NF-κB and HIF-1α proteins.Conclusions IL-6 plays a critical role in CARAS, with the HIF-1α signaling pathway being significant in AR-AS interaction. These findings offer insights and potential biomarkers for future CARAS research and treatment.