We hypothesize that there is a unifying mechanism associated with acute or chronic factors that damage the impermeability barrier that normally protects the bladder. Thus, we propose that increased permeability of the bladder is a root cause of many benign bladder diseases. (1) In bladder regeneration, the race between healing and fibrosis is tipped in favor of fibrosis by permeability of the nascent organ to urine, and we will investigate with animal models how decreasing permeability of the regenerating bladder facilitates healing. (2) In IC/PBS, depolarization of sensory nerves and structural changes induced by leakiness underlie that pathology. Comorbidity studies suggest that a reciprocal relationship exists between bowel and bladder such that changes in one induces permeability changes in the other, and animal studies of this reciprocity will reveal mechanisms relevant to clinical populations. Increased permeability may be a factor in OAB as well. We, therefore, plan a clinical study to determine the role of increased permeability in IC/PBS and CPP and LUTS as a function of aging.

Public Health Relevance

At the end of two years, we will be positioned to have an interdisciplinary basic and clinical research program that is integrated with the Neuroscience and Aging Centers at OUHSC and will address important clinical problems in Urology, which will ultimately improve quality of life in patient populations plagued by bladder diseases that will, in turn, decrease health care costs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory Grants (P20)
Project #
5P20DK097799-02
Application #
8566183
Study Section
Special Emphasis Panel (ZDK1-GRB-6)
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
2
Fiscal Year
2013
Total Cost
$300,000
Indirect Cost
$100,000
Name
University of Oklahoma Health Sciences Center
Department
Type
DUNS #
878648294
City
Oklahoma City
State
OK
Country
United States
Zip Code
73117
Towner, Rheal A; Wisniewski, Amy B; Wu, Dee H et al. (2016) A Feasibility Study to Determine Whether Clinical Contrast Enhanced Magnetic Resonance Imaging can Detect Increased Bladder Permeability in Patients with Interstitial Cystitis. J Urol 195:631-8
Greenwood-Van Meerveld, Beverley; Mohammadi, Ehsan; Tyler, Karl et al. (2015) Mechanisms of Visceral Organ Crosstalk: Importance of Alterations in Permeability in Rodent Models. J Urol 194:804-11
Towner, Rheal A; Smith, Nataliya; Saunders, Debra et al. (2015) Contrast enhanced magnetic resonance imaging as a diagnostic tool to assess bladder permeability and associated colon cross talk: preclinical studies in a rat model. J Urol 193:1394-400
Towner, R A; Smith, N; Saunders, D et al. (2015) Assessment of colon and bladder crosstalk in an experimental colitis model using contrast-enhanced magnetic resonance imaging. Neurogastroenterol Motil 27:1571-9
Hurst, Robert E; Meerveld, Beverley Greenwood-Van; Wisniewski, Amy B et al. (2015) Increased bladder permeability in interstitial cystitis/painful bladder syndrome. Transl Androl Urol 4:563-571
Mondalek, Fadee G; Fung, Kar-Ming; Yang, Qing et al. (2015) Temporal expression of hyaluronic acid and hyaluronic acid receptors in a porcine small intestinal submucosa-augmented rat bladder regeneration model. World J Urol 33:1119-28
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Marentette, John O; Hauser, Paul J; Hurst, Robert E et al. (2013) Tryptase activation of immortalized human urothelial cell mitogen-activated protein kinase. PLoS One 8:e69948