Defective Tamm-Horsfall Protein in Patients With Interstitial Cystitis

Parsons, C. Lowell; Stein, Paul C.; Zupkas, Paul; Chenoweth, Marianne; Argade, Sulabha; Proctor, Jeffrey; Datta, Anup; Trotter, Renée

doi:10.1016/j.juro.2007.07.125

Cited by 29 publications

(26 citation statements)

References 21 publications

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“…The CYP‐induced elevated concentrations of occluding observed in our studies could have changed the functioning of the tight junctions in urothelium, leading to the disturbed permeability. Similarly, expression of T‐H protein and HPX is changed in interstitial cystitis/painful bladder syndrome . T‐H protein plays an important cytoprotective role in the inflammatory processes in the bladder, and HPX belongs to the acute‐phase proteins.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, expression of T-H protein and HPX is changed in interstitial cystitis/painful bladder syndrome. 14,15 T-H protein plays an important cytoprotective role in the inflammatory processes in the bladder, and HPX belongs to the acute-phase proteins. The urinary bladder levels of these both proteins were decreased after CYP administration to the tested rats.…”

Section: Discussionmentioning

confidence: 99%

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Intravesical administration of blebbistatin prevents cyclophosphamide‐induced toxicity of the urinary bladder in female Wistar rats

Wróbel

Serefko

Bańczerowska‐Górska

et al. 2019

Neurourology and Urodynamics

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Aims The main goal of our study was to investigate whether blebbistatin would prevent the cyclophosphamide (CYP)‐induced changes in cystometric and inflammatory parameters indicating the development of bladder inflammation and bladder overactivity. As the nature of CYP‐induced urotoxicity is inflammatory, we assume that agents presenting an anti‐inflammatory potential, such as blebbistatin, are worth special attention. Materials and Methods The experiments were carried out in female Wistar rats. Surgical procedures, cystometric investigations, measurements of bladder edema and urothelium thickness as well as biochemical analyses were performed according to the published literature. Results As expected, an acute administration of CYP (200 mg/kg, intraperitoneally) induced changes in the cystometric parameters and the levels of the tested biomarkers (ie, interleukin 1‐β, interleukin 6, interleukin 10, tumor necrosis factor‐α, nerve growth factor, brain‐derived neurotrophic factor, heparin‐binding epidermal growth factor‐like growth factor, insulin‐like growth factor‐binding protein 3, C‐X‐C motif chemokine 10, orosomucoid‐1, Tamm‐Horsfall protein, hemopexin, and occludin), indicating the development of bladder overactivity and bladder inflammation, respectively. These changes were accompanied by bladder edema and increased urothelium thickness. Intravesical infusion of blebbistatin for 7 days (125 nmol/day) prevented all symptoms of the CYP‐induced urotoxicity. Conclusions Blebbistatin might be a promising novel agent for the treatment of bladder dysfunctions, like CYP‐induced hemorrhage cystitis or bladder overactivity, since it diminished the increased urinary bladder levels of proinflammatory markers and normalized the concentrations of the anti‐inflammatory ones. This effect was accompanied by amelioration of bladder edema and permeability, and normalization of both urothelium thickness and values of the cystometric parameters.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Intravesical administration of blebbistatin prevents cyclophosphamide‐induced toxicity of the urinary bladder in female Wistar rats

Wróbel

Serefko

Bańczerowska‐Górska

et al. 2019

Neurourology and Urodynamics

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“…Defective Tamm-Horsfall protein found in patients with interstitial cystitis (Parsons, et al, 2007) Mice deficient in β-1,4-Gal-transferase develop IgA nephropathy-like disease (Nishie, et al, 2007) Liver fibrosis Serum glycoproteins PNGase F, TOF (s-DHB)…”

Section: Trypsin Tof (Dhb) O-glycansmentioning

confidence: 99%

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2007–2008

Harvey

2011

Mass Spectrometry Reviews

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This review is the fifth update of the original review, published in 1999, on the application of MALDI mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2008. The first section of the review covers fundamental studies, fragmentation of carbohydrate ions, use of derivatives and new software developments for analysis of carbohydrate spectra. Among newer areas of method development are glycan arrays, MALDI imaging and the use of ion mobility spectrometry. The second section of the review discusses applications of MALDI MS to the analysis of different types of carbohydrate. Specific compound classes that are covered include carbohydrate polymers from plants, N- and O-linked glycans from glycoproteins, biopharmaceuticals, glycated proteins, glycolipids, glycosides and various other natural products. There is a short section on the use of MALDI mass spectrometry for the study of enzymes involved in glycan processing and a section on the use of MALDI MS to monitor products of the chemical synthesis of carbohydrates with emphasis on carbohydrate-protein complexes and glycodendrimers. Corresponding analyses by electrospray ionization now appear to outnumber those performed by MALDI and the amount of literature makes a comprehensive review on this technique impractical. However, most of the work relating to sample preparation and glycan synthesis is equally relevant to electrospray and, consequently, those proposing analyses by electrospray should also find material in this review of interest.

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“…Although total levels of THP are unchanged, patients with interstitial cystitis have only half of the THP sialic acid content of healthy controls 25 . Similarly, mass spectrometry of urine THP from kidney stone patients revealed >20% less sialic acid content than healthy controls 26 .…”

Section: Discussionmentioning

confidence: 95%

Tamm–Horsfall glycoprotein engages human Siglec‐9 to modulate neutrophil activation in the urinary tract

et al. 2017

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Urinary tract infections (UTI) are a major problem in human medicine for which better understanding of native immune defenses may reveal new pathways for therapeutic intervention. Tamm-Horsfall glycoprotein (THP), the most abundant urinary protein, interacts with bacteria including uropathogenic E. coli (UPEC) as well host immune cells. In addition to its well-studied functions to antagonize bacterial colonization, we hypothesize that THP serves a critical host defense function through innate immune modulation. Using isolated human neutrophils, we found that THP binds neutrophils and that this interaction reduces reactive oxygen species generation, chemotaxis, and killing of UPEC. We discovered that THP engages the inhibitory neutrophil receptor sialic acid-binding Ig-like lectin-9 (Siglec-9), and mouse functional ortholog Siglec-E, in a manner dependent on sialic acid on its N-glycan moieties. THP-null mice have significantly more neutrophils present in the urine compared to WT mice, both with and without the presence of inflammatory stimuli. These data support THP as an important negative regulator of neutrophil activation in the urinary tract, with dual functions to counteract bacterial colonization and suppress excessive inflammation within the urinary tract.

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Defective Tamm-Horsfall Protein in Patients With Interstitial Cystitis

Abstract: Tamm-Horsfall protein is qualitatively different in patients with interstitial cystitis compared to controls. These data suggest that altered Tamm-Horsfall protein may be involved in interstitial cystitis pathogenesis and it may be useful for clinical diagnosis.

Cited by 29 publications

References 21 publications

Intravesical administration of blebbistatin prevents cyclophosphamide‐induced toxicity of the urinary bladder in female Wistar rats

Intravesical administration of blebbistatin prevents cyclophosphamide‐induced toxicity of the urinary bladder in female Wistar rats

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2007–2008

Tamm–Horsfall glycoprotein engages human Siglec‐9 to modulate neutrophil activation in the urinary tract

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