Potential Biomarkers for Diagnosis of Overactive Bladder Patients: Urinary Nerve Growth Factor, Prostaglandin E2, and Adenosine Triphosphate

Suh, Yoon Seok; Ko, Kwang Jin; Kim, Tae Heon; Lee, Hyo Serk; Sung, Hyun Hwan; Cho, Won Jin; Lee, Munjae; Lee, Kyu-Sung

doi:10.5213/inj.1732728.364

Cited by 13 publications

(8 citation statements)

References 34 publications

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“…In addition to its role as a physical barrier, the urothelium provides bi-directional communication with underlying primary afferents (Lazzeri, 2006; Birder and Andersson, 2013; Merrill et al, 2016) via the detection and/or release of a range of excitatory and inhibitory neurotransmitters and neuromodulators including ATP, acetylcholine, nitric oxide (NO), NGF, prostaglandin E2 (PGE2), neurokinin A, and inflammatory mediators as described above (and extensively reviewed by Birder et al) (Everaerts et al, 2010a,b; Birder and Andersson, 2013; de Groat and Yoshimura, 2015; Grundy et al, 2018a). Altered urothelial mediator release has been identified from OAB and IC/PBS patients in a number of studies and may be a compounding mechanism in the development of chronic neuronal hypersensitivity (Kim et al, 2005, 2006; Sun and Chai, 2006; Suh et al, 2017).…”

Section: Urothelial Permeabilitymentioning

confidence: 99%

Mechanisms Underlying Overactive Bladder and Interstitial Cystitis/Painful Bladder Syndrome

2018

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The bladder is innervated by extrinsic afferents that project into the dorsal horn of the spinal cord, providing sensory input to the micturition centers within the central nervous system. Under normal conditions, the continuous activation of these neurons during bladder distension goes mostly unnoticed. However, for patients with chronic urological disorders such as overactive bladder syndrome (OAB) and interstitial cystitis/painful bladder syndrome (IC/PBS), exaggerated bladder sensation and altered bladder function are common debilitating symptoms. Whilst considered to be separate pathological entities, there is now significant clinical and pre-clinical evidence that both OAB and IC/PBS are related to structural, synaptic, or intrinsic changes in the complex signaling pathways that mediate bladder sensation. This review discusses how urothelial dysfunction, bladder permeability, inflammation, and cross-organ sensitisation between visceral organs can regulate this neuroplasticity. Furthermore, we discuss how the emotional affective component of pain processing, involving dysregulation of the HPA axis and maladaptation to stress, anxiety and depression, can exacerbate aberrant bladder sensation and urological dysfunction. This review reveals the complex nature of urological disorders, highlighting numerous interconnected mechanisms in their pathogenesis. To find appropriate therapeutic treatments for these disorders, it is first essential to understand the mechanisms responsible, incorporating research from every level of the sensory pathway, from bladder to brain.

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Section: Urothelial Permeabilitymentioning

confidence: 99%

Mechanisms Underlying Overactive Bladder and Interstitial Cystitis/Painful Bladder Syndrome

2018

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“…Therefore, ROC analysis suggested that ROCK2, especially in combination with GEF or ADRB3, could act as an auxiliary biomarker for the diagnosis of OAB. Nerve growth factor [ 18 ] and brain-derived neurotrophic factor [ 19 ] have also both been proposed as potentially useful biomarkers for OAB patients. However, the potential of a relationship between urinary neurotrophins and the diagnosis of OAB has not yet been clarified.…”

Section: Discussionmentioning

confidence: 99%

ADRB3, ROCK2, and GEF Levels in Overactive Bladder Patients

Fırat

Aybek

2022

Int Neurourol J

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Purpose: The aim of this study was to evaluate changes in levels of adrenergic receptor β3 (ADRB3), Rho-related kinase 2 (ROCK2), and guanine nucleotide exchange factor (GEF), which play key roles in the adrenergic and cholinergic pathways of contraction-relaxation harmony in voiding physiology, and to explore the relationship between these proteins and overactive bladder (OAB).Methods: This study included 60 idiopathic OAB patients and a healthy control group. A validated OAB-validated 8 questionnaire was completed by all participants. Serum levels of ADRB3, ROCK2, and GEF were examined with enzyme-linked immunosorbent assays. Patient and control groups were compared in terms of these levels, and receiver operating characteristic (ROC) curves were generated for all parameters.Results: The levels of ROCK2 were significantly elevated, but there were no correlations between the OAB symptom score and the serum levels of ROCK2, ADRB3, and GEF in OAB patients. In the ROC analysis, ROCK2 alone provided the strongest potential relationship (area under the curve=0.651) with 84.9% sensitivity. The ROCK2+GEF combination provided a satisfactory relationship (AUC=0.755). The AUC for the ADRB3+ROCK2+GEF combination was 0.752, with 64.2% sensitivity and 88.2% specificity.Conclusions: The study results suggest that alterations in serum ROCK2 levels and the use of this parameter in combination with ADRB3 and GEF levels can shed light on the pathophysiology of idiopathic OAB syndrome and provide a new perspective for treatment.

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“…In OAB syndrome, various urine biomarkers were extensively studied to distinguish phenotypes along with the diagnosis [3,4,38,39]. A representative example is nerve growth factor (NGF) and brain-derived neurotrophic factor, a neurotrophin that is produced in the urothelium or smooth muscle cells is widely used as a marker of lower urinary tract dysfunction.…”

Section: Urinary Biomarkers and Microbiome In Overactive Bladdermentioning

confidence: 99%

The Urobiome and Its Role in Overactive Bladder

Bae

Cheng

2022

Int Neurourol J

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Urine is no longer considered to be sterile. After the existence of the microbiome was revealed through metagenomic analysis using next-generation sequencing, the relationship between characteristics of the microbiome and diseases have been studied and published in various journals. A microbiome exists in the urinary tract and is associated with urinary tract infection, malignancy of the genitourinary tract, and lower urinary tract symptoms. Based on the urine sampling method, sampling site, culture method, and sex, the characteristics of the microbiome vary. Most of the <i>Lactobacillus</i> species are identified mainly in women, and various other species are identified in men. These microorganisms can cause or prevent various diseases. Variations in the microbiome are seen in those with and without disease, and an asymptomatic status does not indicate the absence of microbes. This microbiome has been implicated in a variety of lower urinary tract symptoms and diseases, in particular, overactive bladder. The microbiome differs between patients with urgency and urge urinary incontinence and healthy individuals. There are many aspects of the microbiome yet to be studied in relation to other lower urinary tract symptoms.

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Potential Biomarkers for Diagnosis of Overactive Bladder Patients: Urinary Nerve Growth Factor, Prostaglandin E2, and Adenosine Triphosphate

Cited by 13 publications

References 34 publications

Mechanisms Underlying Overactive Bladder and Interstitial Cystitis/Painful Bladder Syndrome

Mechanisms Underlying Overactive Bladder and Interstitial Cystitis/Painful Bladder Syndrome

ADRB3, ROCK2, and GEF Levels in Overactive Bladder Patients

The Urobiome and Its Role in Overactive Bladder

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