Altered glycosylation of Tamm-Horsfall glycoprotein derived from renal allograft recipients leads to changes in its biological function

Wu, Tsai-Hung; Hsieh, Song-Chou; Li, Ko-Jen; Wu, Cheng-Han; Yu, Chia‐Li; Yang, An-Hang; Tsai, Chang-Youh

doi:10.1016/j.trim.2007.07.001

Cited by 12 publications

(13 citation statements)

References 48 publications

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“…Previous reports indicate that THP is extensively modified with N -linked glycans and may also have O -linked structures during pregnancy [58]–[60]. A variety of strategies to reduce the inclusion of THP in uEV samples have been reported although purification of adequate quantities of THP-free uEVs remains problematic [41], [47], [48].…”

Section: Discussionmentioning

confidence: 99%

Surface Glycosylation Profiles of Urine Extracellular Vesicles

et al. 2013

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Urinary extracellular vesicles (uEVs) are released by cells throughout the nephron and contain biomolecules from their cells of origin. Although uEV-associated proteins and RNA have been studied in detail, little information exists regarding uEV glycosylation characteristics. Surface glycosylation profiling by flow cytometry and lectin microarray was applied to uEVs enriched from urine of healthy adults by ultracentrifugation and centrifugal filtration. The carbohydrate specificity of lectin microarray profiles was confirmed by competitive sugar inhibition and carbohydrate-specific enzyme hydrolysis. Glycosylation profiles of uEVs and purified Tamm Horsfall protein were compared. In both flow cytometry and lectin microarray assays, uEVs demonstrated surface binding, at low to moderate intensities, of a broad range of lectins whether prepared by ultracentrifugation or centrifugal filtration. In general, ultracentrifugation-prepared uEVs demonstrated higher lectin binding intensities than centrifugal filtration-prepared uEVs consistent with lesser amounts of co-purified non-vesicular proteins. The surface glycosylation profiles of uEVs showed little inter-individual variation and were distinct from those of Tamm Horsfall protein, which bound a limited number of lectins. In a pilot study, lectin microarray was used to compare uEVs from individuals with autosomal dominant polycystic kidney disease to those of age-matched controls. The lectin microarray profiles of polycystic kidney disease and healthy uEVs showed differences in binding intensity of 6/43 lectins. Our results reveal a complex surface glycosylation profile of uEVs that is accessible to lectin-based analysis following multiple uEV enrichment techniques, is distinct from co-purified Tamm Horsfall protein and may demonstrate disease-specific modifications.

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Section: Discussionmentioning

confidence: 99%

Surface Glycosylation Profiles of Urine Extracellular Vesicles

et al. 2013

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“…Glycosylation of Tamm-Horsfall glycoprotein is altered, and its various immunomodulatory functions are diminished in renal transplant patients at least in part because of altered NF-B p52 nuclear translocation. 149 …”

Section: Transplantationmentioning

confidence: 99%

Dangers Within

Rosin¹,

Okusa²

2011

Journal of the American Society of Nephrology

247

185

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“…Specifically, uromodulin has been shown to induce pro-inflammatory cytokine release from human whole blood [8], to activate myeloid dendritic cells (DC) to acquire a fully mature DC phenotype [9], and to activate monocytes [8]. Precisely how uromodulin orchestrates these diverse immunological properties is unknown, however the protein has been shown to bind with high affinity to a number of immuno-proteins including the complement factors C1, C1q and C3 [10,11], IgG [12,13] and cytokines such as TNF alpha, IL-1 beta and IL-8 [14]. It is thought that these diverse but potent pro-inflammatory properties of uromodulin may signal tubular damage and repair [8,9].…”

Section: Introductionmentioning

confidence: 99%

Uromodulin Facilitates Neutrophil Migration Across Renal Epithelial Monolayers

Schmid

Prajczer

Grüber

et al. 2010

Cell Physiol Biochem

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The glycosylated protein uromodulin is exclusively found in the thick ascending limb cells (TAL) of the kidney, where it is produced on mass and apically targeted, eventually being secreted into the urine. Recently, there has been a renewed interest in this protein due to its ability to interact with the immune system, implicating this protein as a renal inflammatory molecule. Here we investigated the potential role of membrane bound uromodulin on neutrophil adhesion and trans-epithelial migration. The renal tubular epithelial cell line, LLC-PK1, stably transfected with human uromodulin was used to investigate the influence of uromodulin on neutrophil adherence and migration. Uromodulin expression resulted in a significant increase of neutrophil adherence and trans-epithelial migration, in both the apical to basolateral and the basolateral to apical direction. Although uromodulin is GPI anchored and targeted to the apical membrane, we could also observe expression in the basal and lateral membranes domains, which may be responsible for basolateral to apical migration. Furthermore we show that uromodulin binds both the heavy and light chain of IgG, and that IgG enhances neutrophil migration. This study demonstrates that uromodulin can facilitate neutrophil trans-epithelial migration and that this migration can be amplified by co-factors such as IgG.

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Altered glycosylation of Tamm-Horsfall glycoprotein derived from renal allograft recipients leads to changes in its biological function

Cited by 12 publications

References 48 publications

Surface Glycosylation Profiles of Urine Extracellular Vesicles

Surface Glycosylation Profiles of Urine Extracellular Vesicles

Dangers Within

Uromodulin Facilitates Neutrophil Migration Across Renal Epithelial Monolayers

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