Urothelial Proteome Changes Underlying Overactive Bladder Associated With Bladder Outlet Obstruction

Sep 30, 2026

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Research examines how bladder outlet obstruction–related overactive bladder (OAB) in men with benign prostatic hyperplasia persists after surgical relief by focusing on molecular changes in urothelial tissue. Proteomic profiling from cold-cup biopsies compares OAB and non-OAB groups, using liquid chromatography–tandem mass spectrometry, functional annotation, and pathway enrichment. Results identify 1,510 proteins with 133 differentially expressed, affecting cytoskeletal remodeling, neurotransmitter-related signaling, serotonergic pathways, and immune responses. Findings support disrupted epithelial structure and aberrant signaling, with implications for biomarkers and therapeutic targets.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

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Original Article Int Neurourol J 2025;29(4):226-235 [https://doi.org/10.5213/inj.2550248.124](https://doi.org/10.5213/inj.2550248.124)[ ](https://doi.org/10.5213/inj.2550248.124)pISSN 2093-4777 · eISSN 2093-6931 Urothelial Proteome Changes Underlying Overactive Bladder Associated With Bladder Outlet Obstruction Sang-Yeop Lee1,2*, Ji Yong Lee3*, Sung Ho Yun4, Minji Lee4, Dong-Eon Lee2,4, Ji-Hyeon Min4,5, Chung Lyul Lee3, Gun-Hwa Kim2,4,5, Ju Hyun Shin3 1Biopharmaceutical Research Center, Korea Basic Science Institute, Cheongju, Korea 2Department of Bio-Analytical Science, University of Science and Technology, Daejeon, Korea 3Department of Urology, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, Korea 4Digital Omics Research Center, Korea Basic Science Institute, Cheongju, Korea 5Department of Analytical Science and Technology, Graduate School of Analytical Science and Technology (GRAST), Chungnam National University, Daejeon, Korea 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. Keywords: Urinary bladder, Overactive; Urinary bladder neck obstruction; Proteomics; Urothelium • Grant/Fund Support: This research was supported by Chungnam National University Hospital Research Fund (2022-CF-035), and grants (C270300,C523400, and C539141) from the Korea Basic Science Institute. Corresponding author: Gun-Hwa Kim [https://orcid.org/0000-0003-0360-4435](https://orcid.org/0000-0003-0360-4435)[ ](https://orcid.org/0000-0003-0360-4435)Department of Bio-Analytical Science, University of Science and Technology, Daejeon 34113, Korea [Email: genekgh@kbsi.re.kr](Email: genekgh@kbsi.re.kr) Co-corresponding author: Ju Hyun Shin [https://orcid.org/0000-0001-5996-5876](https://orcid.org/0000-0001-5996-5876)[ ](https://orcid.org/0000-0001-5996-5876)Department of Urology, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, Korea Email: [synthia2000@naver.com](synthia2000@naver.com) *Sang-Yeop Lee and Ji Yong Lee contributed equally to this study as co-first authors. Submitted: September 18, 2025 / Accepted after revision: November

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What key molecular pathways and protein changes were found in OAB patients?

Proteomic analysis identified 1,510 proteins and 133 differentially expressed proteins in OAB versus non-OAB. Dysregulated pathways included cytoskeletal remodeling, Rho GTPase signaling, serotonergic signaling, and immune responses, with structural proteins downregulated and inflammatory mediators upregulated.

Sep 30, 2026

Uploaded by McQueen