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Proteomic profile of an acute partial bladder outlet obstruction.

ABSTRACT: INTRODUCTION:Partial bladder outlet obstruction (pBOO) is a ubiquitous problem in urology. From posterior urethral valves to prostatic hypertrophy, pBOO results in significant morbidity and mortality. However, the pathophysiology is not completely understood. Proteomics uses mass spectrometry to accurately quantify change in tissue protein concentration. Therefore, we have applied proteomic analysis to a rodent model to assess for protein changes after a surgically induced pBOO. We hypothesize that proteomic analysis after an acute obstruction will determine the most prevalent initial protein response and, potentially, novel molecular pathways. METHODS:Sprague Dawley rats underwent a surgically induced pBOO (n = 3 per group) for 3, 7, or 14 days. Bladders were assessed for weight and urodynamic parameters. Proteomics used liquid-chromatography based mass spectrometry. Polymerase chain reaction (PCR) was performed on tissue samples to confirm increased mRNA transcription. RESULTS:Bladder weight and capacity increased over the experimental period, but no changes were seen in bladder pressure. Statistically significant increases in protein quantities were seen in 3 proteins related to endoplasmic reticulum stress: GRP-78 (3.66-fold), RhoA (1.90-fold), and RhoA-GDP (1.95-fold), and 2 cytoskeleton molecules: actin (1.7-fold) and tubulin a/b (3.01-fold). Decorin and lumican, members of the small leucine rich proteoglycan (SLRP) family, were also elevated (0.35- and 0.34-fold, respectively). Real-time PCR data confirmed protein elevation. CONCLUSION:Our experiment confirms that molecular changes occur very soon after the initiation of pBOO, and implicates several molecular pathways. We believe these insights may provide insight into novel prevention and treatment strategies targeted at the pathophysiology of pBOO.

SUBMITTER: Alsaikhan B

PROVIDER: S-EPMC4374996 | biostudies-literature | 2015 Mar-Apr

REPOSITORIES: biostudies-literature

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Proteomic profile of an acute partial bladder outlet obstruction.

Alsaikhan Bader B Fahlman Richard R Ding Jie J Tredget Edward E Metcalfe Peter D PD

Canadian Urological Association journal = Journal de l'Association des urologues du Canada 20150301 3-4

<h4>Introduction</h4>Partial bladder outlet obstruction (pBOO) is a ubiquitous problem in urology. From posterior urethral valves to prostatic hypertrophy, pBOO results in significant morbidity and mortality. However, the pathophysiology is not completely understood. Proteomics uses mass spectrometry to accurately quantify change in tissue protein concentration. Therefore, we have applied proteomic analysis to a rodent model to assess for protein changes after a surgically induced pBOO. We hypot ...[more]

PMID: 25844096

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Project description:PurposePosterior urethral valves are the most common cause of partial bladder outlet obstruction in the pediatric population. However, to our knowledge the etiology and the detailed mechanisms underlying pathological changes in the bladder following partial bladder outlet obstruction remain to be elucidated. Recent findings suggest that hypoxia and associated up-regulation of HIFs (hypoxia-inducible factors) have a key role in partial bladder outlet obstruction induced pathology in the bladder. We examined the effects of pharmacological inhibition of HIF pathways by 17-DMAG (17-(dimethylaminoethylamino)-17-demethoxygeldanamycin) in pathophysiological phenotypes after partial bladder outlet obstruction.Materials and methodsPartial bladder outlet obstruction was surgically created in male C57BL/6J mice. The animals received oral administration of 17-DMAG or vehicle daily starting from the initiation of obstruction up to 5 days. Sham operated mice served as controls. Bladders were harvested from each group 2, 4 and 7 days postoperatively, and analyzed for histological and biochemical changes. Bladder function was assessed by in vitro muscle contractility recordings.ResultsPartial bladder outlet obstruction caused a significant increase in the bladder mass accompanying enhanced collagen deposition in the bladder wall while 17-DMAG treatment suppressed those increases. Treatment with 17-DMAG attenuated the degree of up-regulation of HIFs and their target genes involving the development of tissue fibrosis in obstructed bladders. Treatment with 17-DMAG improved the decreased responses of obstructed bladder strips to electrical field stimulation and KCl.ConclusionsIn vivo 17-DMAG treatment decreased partial bladder outlet obstruction induced pathophysiological changes in the bladder. HIF pathway inhibition has a potential clinical implication for the development of novel pharmacological therapies to treat bladder pathology associated with partial bladder outlet obstruction.

Dataset Information

Proteomic profile of an acute partial bladder outlet obstruction.

Publications

Proteomic profile of an acute partial bladder outlet obstruction.

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