Investigating the Role of microRNAs in the Regulation of Gene Expression and Organ Remodeling During Lower Urinary Tract Dysfunction, Including Bladder Pain Syndrome/Interstitial Cystitis (BPS), and Overactive Bladder Syndrome (OAB)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 103
- Locations
- 1
- Primary Endpoint
- Molecular traits of bladder dysfunction
Study Overview
Brief Summary
Urgency, frequency and incomplete emptying are the key symptoms of lower urinary tract dysfunction, including bladder pain syndrome/interstitial cystitis, and overactive bladder syndrome. Lower urinary tract dysfunction is associated with cellular stress, leading to changes in gene expression and consequent organ remodeling. MicroRNAs are small regulatory molecules, affecting protein synthesis. They are quickly winning recognition as potential therapeutic agents. The investigators will perform a comparative study of mRNAs changed in lower urinary tract dysfunction and address the role of differentially expressed miRNAs in regulation of the genes, important for bladder function. The experimental approach, combining the analysis of human biopsy material with the in vitro cell-based models, will allow the investigators to elucidate the effects of miRNAs on the expression of receptors, contractile proteins and tight junction proteins. Once the disease-induced miRNAs have been characterised and their target genes validated, it will be possible to influence their expression levels thus counter-acting their effects.
The investigators' work addresses fundamental mechanisms of signal transduction in urothelium and smooth muscle during cellular stress caused by inflammation or bladder outlet obstruction, and its regulation in the diseased state. The investigators' findings will further the knowledge of the molecular mechanisms of lower urinary tract dysfunction and have implications for diagnosis and treatment. Additionally, they have relevance for other clinical conditions, where miRNAs are implicated.
Detailed Description
Background
Urgency, frequency and incomplete emptying are the key symptoms of lower urinary tract (LUT) dysfunction, including bladder pain syndrome/interstitial cystitis (BPS), and overactive bladder syndrome (OAB). Detrusor overactivity, which causes the symptoms of overactive bladder syndrome, is commonly observed in patients with bladder outlet obstruction. LUT dysfunction is associated with cellular stress, characterised by changes in cell signalling and the consequent alterations of gene expression leading to organ remodelling. Previously the investigators showed that NK1R-mediated signalling was down-regulated in BPS patients, and implicated microRNAs (miRNAs) in the regulation of NK1R expression and function.
MicroRNAs (miRNAs) are quickly gaining recognition for their role in many biological processes and disease states. MiRNAs are endogenous non-coding single-stranded RNAs which regulate gene expression by post-transcriptional mechanisms. The microRNAs regulate thousands of human gene products, complicating the efforts to predict and functionally validate their targets. Since miRNAs are important for many basic biological processes, any deregulation in their biogenesis or function may develop into a medical condition. Here the investigators propose to investigate the role of miRNAs in gene regulation during LUT disorders.
Chronic BPS is a clinical syndrome characterised by urgency/frequency, pelvic pain and inflammation in the absence of a detectable agent. A multitude of pathogenetic mechanisms have been postulated, but an inflammatory component is commonly thought to be involved. Epithelial damage has often been invoked: the mucinous layer of the healthy bladder is often compromised in patients with BPS. An initiating event (toxin) may cause increased urothelial permeability, which in turn leads to nerve sensitisation. The resulting cell injury propagates, leading to a self-perpetuating inflammatory reaction.
Urgency is a pivotal symptom of the lower urinary tract, and also one of the most bothersome symptoms in men suffering from benign prostatic hyperplasia and the resulting bladder outlet obstruction (BOO). In women OAB is a dynamic disorder, and an estimated 34% of women above 40 experience significant urinary storage symptoms. In contrast to BPS, patients with overactivity do not report bladder pain, although the perception of urgency and the arising discomfort vary between individuals. In order to facilitate diagnosis of BPS and its distinction from DO, and offer specific treatment regimens for each disorder, it is important to unravel the mechanisms behind the pathophysiology of these diseases.
Study Design
- Study Type
- Observational
- Observational Model
- Case Control
- Time Perspective
- Cross Sectional
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •prostate hyperplasia
- •bladder acontractility
- •bladder pain
- •age over 18 years old
- •willingness to participate (informed concent)
- •Exclusion Criteria
- •Age ≤ 18 years old
- •Pregnancy
- •History of or current genito-urinary tuberculosis
- •History of pelvic surgery in the last 6 months
- •History of bladder malignancy, high grade dysplasia or carcinoma in situ
- •sexually transmitted diseases (STD's)
- •Bacteriuria
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Molecular traits of bladder dysfunction
Time Frame: 3 years
Secondary Outcomes
- Protein expression profiling of individual groups(3 years)
- Functional differences between groups(3 years)
- MiRNA expression profiling of individual groups(3 years)