Urinary proteomics evaluation in interstitial cystitis/painful bladder syndrome: a pilot study

Abstract

Purpose: Interstitial cystitis/painful bladder syndrome (IC/PBS) is characterized by chronic pain, pressure and discomfort felt in the pelvis or bladder. An in-depth shotgun proteomics study was carried out to profile the urinary proteome of women with IC/PBS to identify possible specific proteins and networks associated with IC/PBS. Materials and Methods: Urine samples from ten female IC/PBS patients and ten female asymptomatic, healthy control subjects were analyzed in quadruplicate by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on a hybrid linear ion trap-orbitrap mass spectrometer. Gas-phase fractionation (GPF) was used to enhance protein identification. Differences in protein quantity were determined by peptide spectral counting. Results: α-1B-glycoprotein (A1BG) and orosomucoid-1 (ORM1) were detected in all IC/PBS patients, and ≥ 60% of these patients had elevated expression of these two proteins compared to control subjects. Transthyretin (TTR) and hemopexin (HPX) were detected in all control individuals, but ≥ 60% of the IC/PBS patients had decreased expression levels of these two proteins. Enrichment functional analysis showed cell adhesion and response to stimuli were down-regulated whereas response to inflammation, wounding, and tissue degradation were up-regulated in IC/PBS. Activation of neurophysiological processes in synaptic inhibition, and lack of DNA damage repair may also be key components of IC/PBS. Conclusion: There are qualitative and quantitative differences between the urinary proteomes of women with and without IC/PBS. We identified a number of proteins as well as pathways/networks that might contribute to the pathology of IC/PBS or result from perturbations induced by this condition.

Tryptase Activation of Immortalized Human Urothelial Cell Mitogen-Activated Protein Kinase

“…Our in vitro studies indicated enhanced cell proliferation in IC/PBS urothelial cells compared to normal. These data agree with urinary proteomics studies that have identified upregulation of proteins involved in responses to wounding in IC/PBS patients [33]. In vivo , the secretion of APF, or other adaptive responses, may negate any beneficial effect of enhanced ERK 1/2.…”

“…A recently published study [33] used urinary proteomics for normal and IC/PBS patients and identified several proteins and pathways that may contribute to IC/PBS pathology. Data from our laboratory and others suggests that there are biochemical changes that could enhance or impede cell proliferation and differentiation.…”

Human Urine Proteome: A Powerful Source for Clinical Research

“…In 2010, Goo et al [45] analyzed the urinary samples from ten female healthy persons by LC coupled with a hybrid linear ion trap-orbitrap mass spectrometer and identified 1,003 urinary proteins. Li et al [46] used urines from three healthy male donors, and digested peptides were fractionated by two approaches, integrated multidimensional liquid chromatography and Yin-Yang multidimensional liquid chromatography methods.…”

Protection against Heme Toxicity: Hemopexin Rules, OK?

“…Commonly occurring conditions such as interstitial cystitis and painful bladder syndrome (IC/PBS) generate chronic pain, with pressure and discomfort in the pelvis or bladder. Goo et al 221 were interested in discerning not just the proteins whose expression were altered under these conditions but also the pathways and networks that may be coordinately regulated. In their pilot study, of the 78 proteins that were differentially expressed between IC/PBS and controls, α-1 β-glycoprotein and orosomucoid were both increased in more than 60% of the IC/PBS cohort.…”