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

Abstract

SummaryOveractive 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 as a result 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 to 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.

Identification of Immune-Related Genes and Small-Molecule Drugs in Interstitial Cystitis/Bladder Pain Syndrome Based on the Integrative Machine Learning Algorithms and Molecular Docking

“…In addition, GO and KEGG enrichment analysis uncovered evidence that these genes are associated with antimicrobial humoral response, cytokine-cytokine receptor interaction, and the IL-17 signaling pathway. These results align with those obtained in a prior investigation of IC/BPS, suggesting a direct connection between the distinctive genes and the immunological infiltration seen in IC/BPS [29][30][31][32].…”

Slow development of bladder malfunction parallels spinal cord fiber sprouting and interneurons' loss after spinal cord transection

“…Detrusor overactivity and DSD follow similar time-courses, raising the important question if DSD, which causes an obstruction, might be at the basis of detrusor overactivity. In fact, animal models of bladder outlet obstruction (BOO) have been frequently used to investigate detrusor overactivity, since surgical obstruction is enough to drive the emergence of the symptoms over time (Brading, 1997;Park et al, 2018). Proteomic analysis of the urothelium of rats subjected to BOO pointed towards the importance and correlation of detrusor overactivity with an inflammatory response (Park et al, 2018).…”

“…In fact, animal models of bladder outlet obstruction (BOO) have been frequently used to investigate detrusor overactivity, since surgical obstruction is enough to drive the emergence of the symptoms over time (Brading, 1997;Park et al, 2018). Proteomic analysis of the urothelium of rats subjected to BOO pointed towards the importance and correlation of detrusor overactivity with an inflammatory response (Park et al, 2018). Similarly, amount of neurotrophic factors such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) present in the bladder wall have been described to be correlated with the severity of detrusor overactivity (Coelho et al, 2019;Ha et al, 2011), further elucidating the challenges in understating the exact mechanisms underlying overactive bladder.…”

Experimental long-term diabetes mellitus alters the transcriptome and biomechanical properties of the rat urinary bladder

“…A caveat of all transcriptomic analyses is that protein expression may not exactly parallel the spatial and/or temporal changes in the RNA levels. Accordingly, in future, an even more powerful experimental strategy will be to undertake single cell RNA sequencing studies 62 , to correlate levels of individual transcripts with unique tissue compartments, in combination with proteomic analysis 20 , 63 to quantify and locate the many up- or down-regulated molecules in models of diabetic cystopathy.…”