Patients with obstructive or neurogenic lower urinary tract disease will be invited to participate. Upon agreement they will undergo an assessment of bladder function (questionnaires) and bladder biopsies at 2 time-points. Bladder biopsies will be evaluated for molecular changes in the laboratory and compared to the functional findings.By uncovering the molecular similarities and differences between BLUTD and NLUTD, the investigators will elucidate some of the causative factors in the development of these disorders and highlight the impact of myogenic and neurogenic components postulated to be involved. The project involves close collaboration between clinical and basic research.

Population

Controls: patients with cystoscopy for stone disease or microhematuria without bladder symptoms Patients with spinal cord injury or benign prostatic obstruction.

Brief Title

Changes of microRNA Expression in Obstructive and Neurogenic Bladder Dysfunction

Official Title

Changes of microRNA Expression in Obstructive and Neurogenic Bladder Dysfunction Reveal Common Signalling Pathways Relevant for Disease Progression and Recovery

Brief Summary

Patients with obstructive or neurogenic lower urinary tract disease will be invited to <br /> participate. Upon agreement they will undergo an assessment of bladder function <br /> (questionnaires) and bladder biopsies at 2 time-points. Bladder biopsies will be evaluated <br /> for molecular changes in the laboratory and compared to the functional findings.By uncovering <br /> the molecular similarities and differences between BLUTD and NLUTD, the investigators will <br /> elucidate some of the causative factors in the development of these disorders and highlight <br /> the impact of myogenic and neurogenic components postulated to be involved. The project <br /> involves close collaboration between clinical and basic research.

Detailed Description

Lower urinary tract dysfunction (LUTD) has multiple causes including bladder outlet
obstruction (BOO) as a result of benign prostatic hyperplasia (BPH) and neurological diseases
including spinal cord injury (SCI). Manifestations of LUTD include storage symptoms such as
increased daytime frequency, nocturia, urgency and urinary incontinence and voiding symptoms
such as slow stream, hesitancy and incomplete emptying. The consequences of both BOO-induced
(BLUTD) and neurogenic LUTD (NLUTD), leading to functional entities including the low
compliance high pressure bladder as well as the acontractile high volume low pressure
bladder, are believed to share some pathogenetic mechanisms.

In a previous project, the investigators have established micro ribonucleic acid (miRNA) and
messenger ribonucleic acid (mRNA) expression profiles of several urodynamically defined
states of BLUTD. In this follow-up project, the investigators propose to extend these
studies, undertaking a comparative miRNA and RNA profiling of BLUTD and NLUTD, and
investigate the dynamic alteration of microRNA expression in different functional
manifestations of disease. The investigators propose to validate primary gene targets of
miRNAs differentially expressed in urodynamically defined states of BLUTD and identify
signaling pathways, activated during the progression from hypertrophy to decompensation.
Monitoring the reversal of changes in miRNA expression after relief of obstruction and
restoration of normal bladder function will help delineate the key BOO-induced miRNAs with
regulatory potential. Similarly, the dynamics of miRNA alteration, observed in SCI patients
during the development and management of NLUTD should reveal the role of miRNA in gene
expression regulation during neurogenic-induced organ remodelling.

By uncovering the molecular similarities and differences between BLUTD and NLUTD, the
investigators will elucidate some of the causative factors in the development of these
disorders and highlight the impact of myogenic and neurogenic components postulated to be
involved. The project involves close collaboration between clinical and basic research, and
combines the analysis of human biopsy material with in vitro cell-based assays, creating a
comprehensive platform for the dissection of molecular mechanisms of LUTD. This project will
keep the momentum of the investigators' previous research and contribute to the basic and
applied studies into bladder remodeling. It is a logical continuation of their on-going
studies of the role of miRNAs in LUT disorders but represents a novel direction of research
and has high diagnostic and therapeutic potential.

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.