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. 2018 May;17(5):948-960.
doi: 10.1074/mcp.RA117.000290. Epub 2018 Feb 1.

Proteomic Analysis of Urothelium of Rats with Detrusor Overactivity Induced by Bladder Outlet Obstruction

Edmond Changkyun Park  1   2   3 , Jae Sung Lim  4 , Seung Il Kim  1   2   3 , Sang-Yeop Lee  1   2 , Yu-Kyung Tak  1 , Chi-Won Choi  1   5 , Sungho Yun  1 , Joohyun Park  1 , Minji Lee  1   3 , Hyo Kyun Chung  6 , Koon Soon Kim  6 , Yong Gil Na  4 , Ju Hyun Shin  4 , Gun-Hwa Kim  7   3   5
Affiliations

Proteomic Analysis of Urothelium of Rats with Detrusor Overactivity Induced by Bladder Outlet Obstruction

Edmond Changkyun Park et al. Mol Cell Proteomics. 2018 May.

Abstract

Overactive bladder (OAB) syndrome is a condition that has four symptoms: urgency, urinary frequency, nocturia, and urge incontinence and negatively affects a patient's life. Recently, it is considered that the urinary bladder urothelium is closely linked to pathogenesis of OAB. However, the mechanisms of pathogenesis of OAB at the molecular level remain poorly understood, mainly because of lack of modern molecular analysis. The goal of this study is to identify a potential target protein that could act as a predictive factor for effective diagnosis and aid in the development of therapeutic strategies for the treatment of OAB syndrome. We produced OAB in a rat model and performed the first proteomic analysis on the mucosal layer (urothelium) of the bladders of sham control and OAB rats. The resulting data revealed the differential expression of 355 proteins in the bladder urothelium of OAB rats compared with sham subjects. Signaling pathway analysis revealed that the differentially expressed proteins were mainly involved in the inflammatory response and apoptosis. Our findings suggest a new target for accurate diagnosis of OAB that can provide essential information for the development of drug treatment strategies as well as establish criteria for screening patients in the clinical environment.

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Figures

Fig. 1.
Fig. 1.
Representative cystometric tracings in conscious rats. A, Sham-operated rats. Regular voiding patterns, stable basal pressure (BP) and definite threshold pressure (TP) were observed. B, BOO rats with detrusor overactivity (DO). Unstable BP, unremarkable threshold pressure (TP), shortening micturition internal (MI), and increased slope were observed. Values are expressed as intravesical pressure (IVP) (cmH2O) and micturition volume (MV) (ml).
Fig. 2.
Fig. 2.
Identification and quantitative comparison of sham control and OAB rat urothelial proteome. A, Venn diagram that shows the number of identified proteins from the rat urothelium. B, Summary of quantitative analysis of the urothelial proteome from sham control and OAB rats. C, Summary of subcellular localization of 355 differentially expressed proteins between the sham control and OAB rat urothelium.
Fig. 3.
Fig. 3.
Functional annotation of differentially expressed proteins. Three hundred fifty-five differentially expressed proteins between the sham control and OAB rat urothelium were analyzed using the IPA tool. The top 20 most significant canonical pathways in sham control and OAB urothelium were shown.
Fig. 4.
Fig. 4.
Representative protein networks of upstream regulators of OAB. Protein network no.1 (A), network no.3 (B), network no.7 (C) of Table II were shown.
Fig. 5.
Fig. 5.
Protein network analysis with signaling molecules released from the urothelium. IPA-determined network of identified proteins that are associated with signaling molecules released from the urothelium, such as ATP, NO, PG, TAC1, Ach, NGF. Red, up-regulated; green, downregulated.
Fig. 6.
Fig. 6.
Validation of up-regulated proteins in OAB. Western blot (A) and immunohistochemistry (B) of selected proteins in the sham control and OAB bladder urothelium. Uro, urothelium layer; SC, suburothelial connective tissue layer. The scale bar indicates 50 μm (bottom).
See this image and copyright information in PMC

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