'Omics' Approaches to Understanding Interstitial Cystitis/Painful Bladder Syndrome/Bladder Pain Syndrome

You, Sungyong; Yang, Wei; Anger, Jennifer T.; Freeman, Michael R.; Kim, Jayoung

doi:10.5213/inj.2012.16.4.159

Cited by 21 publications

(13 citation statements)

References 77 publications

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“…Important among these challenges is the absence of a consensus on the most physiologically relevant animal models, and the diagnostic and outcome criteria important for establishing the effectiveness of any new drugs [59]. Recent studies of genomic and proteomic approaches suggest that IC has molecular features of both inflammatory and neuronal signaling [60]. Increased tissue levels of inflammatory mediators, cytokines, and high blood levels of acute phase protein such as C-reactive protein were found in IC patients [47].…”

Section: Discussionmentioning

confidence: 99%

Prevention of Anti-microbial Peptide LL-37-Induced Apoptosis and ATP Release in the Urinary Bladder by a Modified Glycosaminoglycan

et al. 2013

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Interstitial cystitis (IC), often referred to in combination with painful bladder syndrome, is a chronic inflammatory disease of the bladder. Current therapies primarily focus on replenishing urothelial glycosaminoglycan (GAG) layer using GAG analogs and managing pain with supportive therapies. However, the elusive etiology of IC and the lack of animal models to study the disease have been major hurdles developing more effective therapeutics. Previously, we showed an increased urinary concentration of antimicrobial peptide LL-37 in spina bifida patients and used LL-37 to develop a mouse model of cystitis that mimics important clinical findings of IC. Here we investigate (1) the molecular mechanism of LL-37 induced cystitis in cultured human urothelial cells and in mice, (2) the protective effects of GM-0111, a modified GAG, within the context of this mechanism, (3) the physiological and molecular markers that correlate with the severity of the inflammation, and (4) the protective effects of several GAGs using these biomarkers in our LL-37 induced cystitis model. We find that LL-37 quickly induces release of ATP and apoptosis in the urothelium. These changes can be inhibited by a chemically-modified GAG, GM-0111. Furthermore, we also find that GAG analogs provide varying degrees of protection against LL-37 challenge in mice. These findings suggest that GM-0111 and possibly GAG molecules prevent the development of cystitis by blocking the apoptosis and the concurrent release of ATP from the urothelium.

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Section: Discussionmentioning

confidence: 99%

Prevention of Anti-microbial Peptide LL-37-Induced Apoptosis and ATP Release in the Urinary Bladder by a Modified Glycosaminoglycan

et al. 2013

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“…It is difficult to assess whether the estimate of incidence of IC in a 2-year time window is an underestimation or overestimation of IC. The clinical diagnosis of IC is challenging, because its symptoms are similar to those of other disorders of the bladder and there is no definite test to identify IC [20]. Furthermore, we do not know how healthcare providers utilized the codes we used in this study to define IC, and no validation studies have been conducted to assess how sensitive or specific the concepts used are.…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Interstitial Cystitis in the General Population and in Individuals With Depression

et al. 2019

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Purpose To identify risk factors for interstitial cystitis (IC), a chronic bladder disorder that may have a significant detrimental impact on quality of life, in the general population and in individuals with depression. Methods This was a comparative study using a US claims database. Adults who had records of a visit to the health system in 2010 or later were included. The outcome was the development of IC within 2 years after the index date. The index date for the general population was the first outpatient visit, and for individuals with depression, it was the date of the diagnosis of depression. IC was defined using the concepts of ulcerative and IC. We included all medical conditions present any time prior to the index visit as potential risk factors. Results The incidence of IC was higher in individuals with depression than in the general population. Of the 3,973,000 subjects from the general population, 2,293 (0.06%) developed IC within 2 years. Of the 249,200 individuals with depression, 320 (0.13%) developed IC. The characteristics of the individuals who developed IC were similar in both populations. Those who developed IC were slightly older, more likely to be women, and had more chronic pain conditions, malaise, and inflammatory disorders than patients without IC. In the general population, subjects who developed IC were more likely to have mood disorders, anxiety, and hypothyroidism. Conclusions The incidence of IC was higher in individuals with depression. Subjects who developed IC had more chronic pain conditions, depression, malaise, and inflammatory disorders.

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“…25 The current state of art among omics and IC is limited to specific markers and genes associated with autoimmune properties. 26 At the molecular level, previous studies conducted by Keay et al 27 demonstrated that a small glycopeptide named antiproliferative factor (APF) is a urinary biomarker of IC with high sensitivity and specificity (94% and 95% respectively, p < 0.005). APF inhibits urothelial cells proliferations, increasing urothelium permeability and it's secreted specifically by bladder epithelial cells from patients with this disorder.…”

Section: Interstitial Cystitis (Ic)/bladder Pain Syndrome (Bps)mentioning

confidence: 99%

Omics in urology: An overview on concepts, current status and future perspectives

et al. 2021

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Recent technological advances in molecular biology have led to great progress in the knowledge of structure and function of cells and their main constituents. In this setting, ‘omics’ is standing out in order to significantly improve the understanding of etiopathogenetic mechanisms of disease and contribute to the development of new biochemical diagnostics and therapeutic tools. ‘Omics’ indicates the scientific branches investigating every aspect of cell’s biology, including structures, functions and dynamics pathways. The main ‘omics’ are genomics, epigenomics, proteomics, transcriptomics, metabolomics and radiomics. Their diffusion, success and proliferation, addressed to many research fields, has led to many important acquisitions, even in Urology. Aim of this narrative review is to define the state of art of ‘omics’ application in Urology, describing the most recent and relevant findings, in both oncological and non-oncological diseases, focusing the attention on urinary tract infectious, interstitial cystitis, urolithiasis, prostate cancer, bladder cancer and renal cell carcinoma. In Urology the majority of ‘omics’ applications regard the pathogenesis and diagnosis of the investigated diseases. In future, its role should be implemented in order to develop specific predictors and tailored treatments.

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'Omics' Approaches to Understanding Interstitial Cystitis/Painful Bladder Syndrome/Bladder Pain Syndrome

Cited by 21 publications

References 77 publications

Prevention of Anti-microbial Peptide LL-37-Induced Apoptosis and ATP Release in the Urinary Bladder by a Modified Glycosaminoglycan

Prevention of Anti-microbial Peptide LL-37-Induced Apoptosis and ATP Release in the Urinary Bladder by a Modified Glycosaminoglycan

Risk Factors for Interstitial Cystitis in the General Population and in Individuals With Depression

Omics in urology: An overview on concepts, current status and future perspectives

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