Bioinformatic analysis reveals the molecular mechanisms of Trefoil factor 3 involved in asthma pathogenesis

Objective Investigate the expression, regulatory network and function of TFF3 in asthma from a multi-omics perspective through bioinformatics and cellular experiments to provide clues for understanding its molecular mechanisms in asthma. Methods Downloaded two asthma-related datasets (GSE67472 and GSE147878) from GEO. Conducted differential expression analysis and WGCNA to find common genes related to asthma phenotype and TFF3 expression. Constructed a PPI network to identify key genes interacting with TFF3. Performed GO and pathway enrichment analysis using DAVID. Analyzed the relationship between TFF3 and immune cell infiltration with CIBERSORTx. Used molecular docking to validate interactions. In vitro, induced 16HBE cells with HDM to establish asthma model and detected inflammatory indicators and TFF3 by RT-qPCR and western blotting. Results TFF3 expression was significantly increased in asthma patients in both datasets. ROC analysis showed good diagnostic specificity and sensitivity. 57 co-expressed genes related to asthma and TFF3 were screened, with 11 genes directly interacting with TFF3 and upregulated. Functional enrichment analysis indicated involvement in asthma-related processes. Immune infiltration analysis showed increased M2 macrophages and mast cells, decreased M1 macrophages, and positive correlation with TFF3. Molecular docking confirmed stable binding. In vitro experiments showed increased inflammation index and TFF3 expression after HDM intervention. Conclusion The study used bioinformatics and cellular experiments to show TFF3’s key roles in asthma pathogenesis in aspects like gene expression, protein interaction, and immune microenvironment. TFF3 may regulate genes like AGR2 and AKT1, affect immune cells, and be involved in processes like cell migration and immune response. It provides clues for exploring molecular mechanisms and may offer new directions for asthma diagnosis and treatment.