Identification of disulfidptosis-related genes in interstitial cystitis and functional validation of SLC7A11 in urothelial barrier dysfunction

Objective Interstitial cystitis (IC) is a chronic bladder disorder characterized by pelvic pain and urinary frequency, but its molecular mechanisms remain incompletely understood. Because oxidative stress, cytoskeletal remodeling, and urothelial barrier injury are central features of IC, we investigated whether disulfidptosis-related genes could provide mechanistic clues and candidate biomarkers for IC. Methods Transcriptomic profiles from two IC-related GEO datasets, GSE11783 (10 BPS/IC cases and 6 controls) and GSE28242 (8 BPS/IC cases and 5 controls), were integrated after batch correction. Differential expression, GO/KEGG/GSEA enrichment analyses, ssGSEA and MCPcounter immune infiltration analyses, qPCR and Western blot validation in human bladder tissues, and in vitro SV-HUC-1 assays (CCK-8, TEER, FITC-dextran permeability, ZO-1 immunofluorescence, ELISA, and NF-κB pathway Western blotting) were used to identify and functionally evaluate DRDEGs. Results Comparative analysis identified 4400 differentially expressed genes between IC and normal samples. Five DRDEGs (CAPZB, ACTB, FLNB, MYL6, and SLC7A11) showed significant differential expression, were enriched in oxidative stress, cell adhesion, actin cytoskeleton, and tight junction-related processes, and demonstrated moderate diagnostic performance. Immune infiltration analysis linked DRDEGs with multiple immune and stromal populations. Functional experiments demonstrated that SLC7A11 knockdown improved cell viability and barrier integrity, increased TEER, reduced FITC-dextran permeability, preserved ZO-1 continuity, and dampened NF-κB-mediated inflammation, including reduced p-p65/p-IKKα activation and lower TNF-α/IL-6 release. Conclusion This study integrates bioinformatic analyses with functional validation to identify disulfidptosis-related genes involved in IC. Our findings highlight SLC7A11 as a preliminary candidate linking disulfidptosis-related gene signatures with inflammation-associated urothelial barrier dysfunction, suggesting that it may serve as a potential biomarker and therapeutic target that warrants further validation.