Urothelial Proteome Changes Underlying Overactive Bladder Associated With Bladder Outlet Obstruction

Abstract

Purpose: Overactive bladder (OAB) in men with bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH) represents a major therapeutic challenge, as symptoms often persist even after surgical relief of obstruction. The underlying molecular mechanisms, however, remain poorly defined. The aim of this study was to identify differentially expressed proteins in the urothelial tissues of patients with BOO-related OAB using a proteomic approach. Methods: Bladder urothelial tissues were obtained via cold-cup biopsy during transurethral resection of the prostate in patients with BPH. Patients were classified into OAB and non-OAB groups. Proteomic profiling was conducted using liquid chromatography–tandem mass spectrometry, followed by functional annotation and pathway enrichment analyses with the Ingenuity Pathway Analysis and Gene Ontology tools. Results: Proteomic analysis identified 1,510 proteins, of which 133 were differentially expressed proteins in patients with OAB compared with the non-OAB group. Dysregulated pathways included cytoskeletal remodeling, Rho GTPase signaling, serotonergic signaling, and immune responses. Structural proteins such as ACTA2, CFL2, MYLK, and PPP1R12B were markedly downregulated, whereas GNA13 and multiple inflammatory mediators were upregulated. Functional analysis confirmed the enrichment of neurotransmitter catabolic processes, immune responses, and impaired cell-cell contact, suggesting structural disorganization and aberrant epithelial signaling in the OAB group. Conclusions: BOO-related OAB is associated with distinct molecular disturbances in cytoskeletal organization, neurotransmitter pathways, and immune responses. These proteomic findings provide novel insights into disease pathophysiology and highlight potential molecular targets for biomarker discovery and therapeutic interventions.