Identification of inflammation-related biomarkers and therapeutic targets for neurogenic bladder fibrosis via multi-omics analysis.

Inflammatory responses play a crucial role in the progression of pediatric neurogenic bladder (NB)-associated fibrosis; however, their specific contributions remain poorly understood. This study aimed to identify inflammation-related biomarkers for diagnosing NB fibrosis and to explore potential therapeutic drugs. The NB rat model was established by spinal nerve severing, followed by single-cell and bulk RNA sequencing of bladder tissues. Through integrated analysis-including differentially expressed genes (DEGs), inflammation-related genes (IRGs), WGCNA, and machine learning-we identified four diagnostic biomarkers: HIF-1α, IL-1β, CD40, and IL10RA. Molecular biology experiments validated the elevated expression of these biomarkers in NB patients. Single-cell RNA sequencing further localized their overexpression to epithelial cells, interstitial cells, and T cells. Connectivity Map (cMAP) analysis identified the MEK inhibitor PD-0325901 as a potential anti-fibrotic agent, which was subsequently confirmed through in vivo and in vitro experiments. Molecular docking simulations demonstrated that PD-0325901 exerts its therapeutic effects by targeting HIF-1α. Collectively, our findings not only provide novel diagnostic biomarkers for NB fibrosis but also propose PD-0325901 as a promising candidate for the treatment of fibrosis.