Potential urine and serum biomarkers for patients with bladder pain syndrome/interstitial cystitis

Abstract

Abbreviations & Acronyms APF = antiproliferative factor BPS/IC = bladder pain syndrome/interstitial cystitis BUC = bladder urothelial cells CRP = C-reactive protein EGF = epidermal growth factor GP51 = glycoprotein 51 HB-EGF = heparin binding growth factor-like growth factor IC = interstitial cystitis IL = interleukin MCP-1 = monocyte chemotactic protein-1 MIP-1β = macrophage inflammatory protein OAB = overactive bladder NGF = nerve growth factor NIDDK = National Institute of Diabetes, Digestive, and Kidney Diseases TNF-α = tumor necrosis factor-α ZO-1 = zonula occludens-1 Abstract: There is a lack of consensus on the pathophysiology of bladder pain syndrome/ interstitial cystitis. The chronic pain symptoms of bladder pain syndrome/interstitial cystitis refractory to local treatment could be a result of central nervous system sensitization and persisting abnormalities in the bladder wall, which activate the afferent sensory system. Evidence also shows that bladder pain syndrome/interstitial cystitis is a heterogeneous syndrome and that the two subtypes, the ulcerative (classic) and non-ulcerative types, represent different disease entities. There is a need for non-invasive markers for the differential diagnoses of the subtypes of bladder pain syndrome/interstitial cystitis, and between bladder pain syndrome/interstitial cystitis and bladder sensory disorders, such as hypersensitive bladder syndrome or overactive bladder. Bladder pain syndrome/interstitial cystitis, but not overactive bladder, involves an aberrant differentiation program in the bladder urothelium that leads to altered synthesis of several proteoglycans, cell adhesion and tight junction proteins, and bacterial defense molecules. These findings have led to the rationale for identifying urinary biomarkers to detect bladder pain syndrome/interstitial cystitis in patients with frequency urgency syndrome. Recently, the markers that have been the focus of the most research are antiproliferative factor, epidermal growth factor, heparin-binding epidermal growth factor, glycosaminoglycans and bladder nitric oxide. In addition, inflammatory proteins in the urine and serum play important roles in the pathogenesis of bladder pain syndrome/interstitial cystitis. The urinary proteome is an easily accessible source of biomarkers for differentiation between inflammatory bladder disorders. Analysis of multiple urinary proteins and serum cytokines could provide a diagnostic basis for bladder pain syndrome/interstitial cystitis, and could be a tool for the differential diagnosis of bladder pain syndrome/interstitial cystitis and other sensory bladder disorders.

Mesenchymal Stem Cell Therapy Alleviates Interstitial Cystitis by Activating Wnt Signaling Pathway

“…We next examined the histological features observed in the IC patients, including epithelium denudation, abnormal increases in inflammation, neurofilament production, and angiogenesis [34,35]. Compared with the sham-operated rats, the bladder tissues in the IC group demonstrated severe inflammation ( Fig.…”

“…Although the etiology and pathogenesis of IC remain unclear, a variety of pathophysiological insults may result in the processes that self-perpetuate epithelial cell dysfunction, C nerve fiber activation, mast cell proliferation, and, ultimately, tissue damage, scarring, fibrosis, and neuropathic pain [34,35]. Among these, impaired epithelial integrity is considered the major trigger for IC, and indeed several abnormities in the urothelium have been described using bladder biopsies and cultured urothelial cells obtained from IC patients.…”

Stress and Chronic Pelvic Pain

“…To that end, a number of urine biomarkers are associated with IC/PBS, such as IL-6, 121-124 histamine, 123 and NGF. 125,126 A substantial percentage ($25%) of IC/PBS patients report a history of childhood sexual or physical abuse, which can significantly affect presentation of symptoms, including voiding and urgency. 42,[127][128][129] Animal models that incorporate neonatal bladder irritation or stress exposure have been developed to study the effects on bladder sensitivity and function.…”

Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Male Bladder Pain Syndrome/Interstitial Cystitis: How Are They Related?

“…Numerous diagnostic biomarkers for BPS/IC have been explored, including antiproliferative factor, urinary and serum nerve growth factors, and urinary and serum proinflammatory cytokines or chemokines. However, none of these putative biomarkers have been validated [33]. Potassium chloride bladder permeability test is no longer recommended, as it lacks sufficient evidence in its effectiveness [15].…”