Abnormalities in Expression of Structural, Barrier and Differentiation Related Proteins, and Chondroitin Sulfate in Feline and Human Interstitial Cystitis

Hauser, Paul; VanGordon, Samuel; Seavey, Jonathan G.; Sofinowski, Troy M.; Ramadan, Mohammad; Abdullah, Shivon N.; Buffington, C.A. Tony; Hurst, Robert E.

doi:10.1016/j.juro.2015.01.090

Cited by 29 publications

(30 citation statements)

References 27 publications

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“…Multiple studies tried to explain the pathogenesis of FIC in cats by using animal models (Logadottir et al, 2014;Dogishi et al, 2017) like mice and rats or even by comparing it with human interstitial cystitis (IC) (Hauser et al, 2015). In fact, some of these studies revealed a part of the pathophysiology of the syndrome, yet still investigating the disease condition in naturally-occurring model of IC in cats may permit more accurate results than those obtained by acute models of inflammation/injury of the bladder in healthy animals.…”

Section: Research Articlementioning

confidence: 99%

Alterations of Pro-Inflammatory Cytokines and Tissue Protein Expressions in Cats with Interstitial Cystitis

Mohamaden¹

2019

PVJ

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Feline interstitial cystitis (FIC) is a chronic disease of the urinary system in cats. Our main objective is to investigate the concurrent changes in serum, urine and at the bladder tissue level in FIC affected cats which might provoke the observed clinical signs. Twelve adult cats were used in this study, six cats were suffering from signs of feline lower urinary tract dysfunction (FLUTD) and the other six were clinically healthy and served as the control group. All cats were clinically examined. Serum and urine samples were collected and tested for IL-6, IL-1 β, TNF-α level while total nitric oxide (TNO) was additionally tested in urine. Bladder tissue specimens were obtained for histopathological examination and immunohistochemical expression of mast cells (MC) tryptase, vasoactive growth factor-A (VAGF-A), E-cadherin and plasma glycoprotein (P-gp). There were significant increases in the serum levels of IL-6, IL-1β, and TNF-α and in the urinary levels of IL-6, IL-1 β of affected cats in comparison to the control healthy ones. The immunohistochemical technique revealed a marked increase in the MC tryptase and VAGF-A in the bladder tissue of FIC cats compared to the control group, while Ecadherin and p-glycoprotein were significantly decreased. We concluded that mast cells and its released mediators play an important role in the pathogenesis of the interstitial cystitis in cats.To Cite This Article: Mohamaden WI, Hamad R and Bahr HI, 2019. Alterations of pro-inflammatory cytokines and tissue protein expressions in cats with interstitial cystitis. Pak Vet J, 39(2): 151-156. http://dx.

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Section: Research Articlementioning

confidence: 99%

Alterations of Pro-Inflammatory Cytokines and Tissue Protein Expressions in Cats with Interstitial Cystitis

Mohamaden¹

2019

PVJ

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“…Edema, inflammatory cells (e.g., lymphocytes, eosinophils, neutrophils), and disruptions of the mucosa, submucosa, and muscular tissue were recorded. Immunohistochemistry and immunofluorescence were performed as previously described (10,26). Controls included a known positive for each antibody, a negative control omitting the primary antibody, and for the ChABC-treated rat bladders the slide was not treated with ChABC to demonstrate the epitope was released by the in vivo treatment.…”

Section: Bladder Histopathology and Immunolabelingmentioning

confidence: 99%

In the absence of overt urothelial damage, chondroitinase ABC digestion of the GAG layer increases bladder permeability in ovariectomized female rats

Hurst

Gordon

Tyler

et al. 2016

American Journal of Physiology-Renal Physiology

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In the absence of overt urothelial damage, chondroitinase ABC digestion of the GAG layer increases bladder permeability in ovariectomized female rats. Am J Physiol Renal Physiol 310: F1074 -F1080, 2016. First published February 24, 2016 doi:10.1152/ajprenal.00566.2015.-Loss of integrity of the protective impermeability barrier in the urothelium has been identified as significant in bladder dysfunction. In this study, we tested the theory that the luminal layer of glycosaminoglycans (GAG) serves as an important component of barrier function. The peptide polycation protamine sulfate (PS), 1 mg/ml, was instilled intravesically for 10 min into rat bladders. Chondroitinase ABC (ChABC), 63 IU/ml, was instilled into an additional six rats for 30 min to digest the GAG layer. Unmanipulated controls and sham-injected controls were also performed. After 24 h, the rats were euthanized, the bladders were removed, and permeability was assessed in the Ussing chamber and by diffusion of FITC-labeled dextran (4 kDa) to measure macromolecular permeability. The status of tight junctions was assessed by immunofluorescence and electron microscopy. In control and sham treated rat bladders, the transepithelial electrical resistance were means of 2.5 Ϯ 1.1 vs. 2.6 Ϯ 1.1 vs 1.2 Ϯ 0.5 and 1.01 Ϯ 0.7 k⍀·cm 2 in the PS-treated and ChABC-treated rat bladders (P ϭ 0.0016 and P ϭ 0.0039, respectively). Similar differences were seen in dextran permeability. Histopathology showed a mild inflammation following PS treatment, but the ChABC-treated bladders were indistinguishable from controls. Tight junctions generally remained intact. ChABC digestion alone induced bladder permeability, confirming the importance of the GAG layer to bladder barrier function and supports that loss of the GAG layer seen in bladder biopsies of interstitial cystitis patients could be a significant factor producing symptoms for at least some interstitial cystitis/painful bladder syndrome patients. urinary bladder; administration; intravesical; cystitis; interstitial; permeability; models; animal INTERSTITIAL CYSTITIS (IC) is a disease of the bladder diagnosed by exclusion on the basis of urgency, frequency, and pain (6). Although the etiology of this disease remains unknown, the evidence suggests that there is disruption of the urothelium that could result in enhanced bladder permeability (9,17,22,31). For the IC patient, the presence of urine is responsible for inflammation and pain in addition to promoting thinning and sloughing of the urothelium and distinct changes in the muscle (21,27,30). A high proportion of IC patients show loss of chondroitin sulfate from the luminal surface of the urothelium as well as abnormalities in uroplakin, the cell adherence protein E-cadherin, and ZO-1, the molecule in the zona occludens that links cells together (9). The identification of comorbitities that appear frequently with IC has suggested that the bladder symptoms are part of a wider spectrum of symptoms denoted by chronic pelvic pain (CPP) or IC/painful bladder syndrome (IC/...

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“…There is a strong and growing body of evidence showing changes in the expression of TJ-associated proteins in biopsies from patients with IC/BPS (Slobodov et al, 2004; Hauser et al, 2008; Sanchez Freire et al, 2010; Lee and Lee, 2014; Hauser et al, 2015). TJs consist of a network of cytosolic and membrane proteins that associate to seal the paracellular space between adjacent epithelial cells just beneath their apical surface.…”

Section: Introductionmentioning

confidence: 99%

Urothelial Tight Junction Barrier Dysfunction Sensitizes Bladder Afferents

Montalbetti

Rued

Taiclet

et al. 2017

eNeuro

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Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic voiding disorder that presents with pain in the urinary bladder and surrounding pelvic region. A growing body of evidence suggests that an increase in the permeability of the urothelium, the epithelial barrier that lines the interior of the bladder, contributes to the symptoms of IC/BPS. To examine the consequence of increased urothelial permeability on pelvic pain and afferent excitability, we overexpressed in the urothelium claudin 2 (Cldn2), a tight junction (TJ)-associated protein whose message is significantly upregulated in biopsies of IC/BPS patients. Consistent with the presence of bladder-derived pain, rats overexpressing Cldn2 showed hypersensitivity to von Frey filaments applied to the pelvic region. Overexpression of Cldn2 increased the expression of c-Fos and promoted the activation of ERK1/2 in spinal cord segments receiving bladder input, which we conceive is the result of noxious stimulation of afferent pathways. To determine whether the mechanical allodynia observed in rats with reduced urothelial barrier function results from altered afferent activity, we examined the firing of acutely isolated bladder sensory neurons. In patch-clamp recordings, about 30% of the bladder sensory neurons from rats transduced with Cldn2, but not controls transduced with GFP, displayed spontaneous activity. Furthermore, bladder sensory neurons with tetrodotoxin-sensitive (TTX-S) action potentials from rats transduced with Cldn2 showed hyperexcitability in response to suprathreshold electrical stimulation. These findings suggest that as a result of a leaky urothelium, the diffusion of urinary solutes through the urothelial barrier sensitizes bladders afferents, promoting voiding at low filling volumes and pain.

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Abnormalities in Expression of Structural, Barrier and Differentiation Related Proteins, and Chondroitin Sulfate in Feline and Human Interstitial Cystitis

Cited by 29 publications

References 27 publications

Alterations of Pro-Inflammatory Cytokines and Tissue Protein Expressions in Cats with Interstitial Cystitis

Alterations of Pro-Inflammatory Cytokines and Tissue Protein Expressions in Cats with Interstitial Cystitis

In the absence of overt urothelial damage, chondroitinase ABC digestion of the GAG layer increases bladder permeability in ovariectomized female rats

Urothelial Tight Junction Barrier Dysfunction Sensitizes Bladder Afferents

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