Tamm-Horsfall Protein

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Ranjan Mascarenhas - One of the best experts on this subject based on the ideXlab platform.

  • tamm horsfall Protein knockout mice are more prone to urinary tract infection rapid communication
    Kidney International, 2004
    Co-Authors: James M Bates, Haja Mohideen Raffi, Krishna Prasadan, Ranjan Mascarenhas
    Abstract:

    Tamm-Horsfall Protein knockout mice are more prone to urinary tract infection. Background Human colon contains many bacteria that commonly colonize the perineum and frequently enter the urinary tract. Uropathogenic Escherichia coli are the most common cause of urinary tract infection. Type 1 fimbriated E. coli have been associated with cystitis, and P fimbriated E. coli with pyelonephritis. Factors involved in clearing bacteria from the urinary tract are poorly understood. Tamm-Horsfall Protein (THP), the most abundant Protein in mammalian urine, has been postulated to play a role in defense against urinary tract infection but definitive proof for this idea has been lacking. Methods In this study, we generated THP gene knockout mice by the technique of homologous recombination, and examined if the THP-deficient (THP -/- ) mice were more prone to urinary tract infection. Various strains of E. coli expressing type 1 or P fimbriae were introduced transurethrally into the bladders of the THP -/- and genetically similar wild-type (THP +/+ ) mice. Urine, bladder, and kidney tissues were obtained from the mice and cultured for bacterial growth. Results THP -/- mice inoculated with type 1 fimbriated E. coli had a longer duration of bacteriuria, and more intense colonization of the urinary bladder in comparison with THP +/+ mice. When inoculated with a P fimbriated strain of E. coli, the THP -/- mice showed no difference in kidney bacterial load when compared with the THP +/+ mice. Conclusion These findings support the idea that THP serves as a soluble receptor for type 1 fimbriated E. coli and helps eliminate bacteria from the urinary tract.

Saeed R. Khan - One of the best experts on this subject based on the ideXlab platform.

  • progressive renal papillary calcification and ureteral stone formation in mice deficient for tamm horsfall Protein
    American Journal of Physiology-renal Physiology, 2010
    Co-Authors: Yan Liu, Saeed R. Khan, David S Goldfarb, Andrew P Evan, Fengxia Liang, John C Lieske
    Abstract:

    Mammalian urine contains a range of macromolecule Proteins that play critical roles in renal stone formation, among which Tamm-Horsfall Protein (THP) is by far the most abundant. While THP is a potent inhibitor of crystal aggregation in vitro and its ablation in vivo predisposes one of the two existing mouse models to spontaneous intrarenal calcium crystallization, key controversies remain regarding the role of THP in nephrolithiasis. By carrying out a long-range follow-up of more than 250 THP-null mice and their wild-type controls, we demonstrate here that renal calcification is a highly consistent phenotype of the THP-null mice that is age and partially gene dosage dependent, but is gender and genetic background independent. Renal calcification in THP-null mice is progressive, and by 15 mo over 85% of all the THP-null mice develop spontaneous intrarenal crystals. The crystals consist primarily of calcium phosphate in the form of hydroxyapatite, are located more frequently in the interstitial space of the renal papillae than intratubularly, particularly in older animals, and lack accompanying inflammatory cell infiltration. The interstitial deposits of hydroxyapatite observed in THP-null mice bear strong resemblances to the renal crystals found in human kidneys bearing idiopathic calcium oxalate stones. Compared with 24-h urine from the wild-type mice, that of THP-null mice is supersaturated with brushite (calcium phosphate), a stone precursor, and has reduced urinary excretion of citrate, a stone inhibitor. While less frequent than renal calcinosis, renal pelvic and ureteral stones and hydronephrosis occur in the aged THP-null mice. These results provide direct in vivo evidence indicating that normal THP plays an important role in defending the urinary system against calcification and suggest that reduced expression and/or decreased function of THP could contribute to nephrolithiasis.

  • Animal models of kidney stone formation: an analysis.
    World Journal of Urology, 1997
    Co-Authors: Saeed R. Khan
    Abstract:

    Calcific kidney stones in both humans and mildly hyperoxaluric rats are located on renal papillary surfaces and consist of an organic matrix and crystals of calcium oxalate and/or calcium phosphate. The matrix is intimately associated with the crystals and contains substances that can promote as well as inhibit calcification. Osteopontin, Tamm-Horsfall Protein, bikunin, and prothrombin fragment 1 have been identified in matrices of both human and rat stones. Hyperoxaluria can provoke calcium oxalate nephrolithiasis in both humans and rats. Kidney-stone-forming rats are hypomagnesuric and hypocitraturic during nephrolithiasis. Human stone formers may have the same disorders. Males of both species are prone to develop calcium oxalate nephrolithiasis, whereas females tend to form calcium phosphate stones. Oxalate metabolism is considered to be almost identical between rats and humans. Thus, there are many similarities between experimental nephrolithiasis induced in rats and human kidney-stone formation, and a rat model of calcium oxalate nephrolithiasis can be used to investigate the mechanisms involved in human kidney stone formation.

John C Lieske - One of the best experts on this subject based on the ideXlab platform.

  • progressive renal papillary calcification and ureteral stone formation in mice deficient for tamm horsfall Protein
    American Journal of Physiology-renal Physiology, 2010
    Co-Authors: Yan Liu, Saeed R. Khan, David S Goldfarb, Andrew P Evan, Fengxia Liang, John C Lieske
    Abstract:

    Mammalian urine contains a range of macromolecule Proteins that play critical roles in renal stone formation, among which Tamm-Horsfall Protein (THP) is by far the most abundant. While THP is a potent inhibitor of crystal aggregation in vitro and its ablation in vivo predisposes one of the two existing mouse models to spontaneous intrarenal calcium crystallization, key controversies remain regarding the role of THP in nephrolithiasis. By carrying out a long-range follow-up of more than 250 THP-null mice and their wild-type controls, we demonstrate here that renal calcification is a highly consistent phenotype of the THP-null mice that is age and partially gene dosage dependent, but is gender and genetic background independent. Renal calcification in THP-null mice is progressive, and by 15 mo over 85% of all the THP-null mice develop spontaneous intrarenal crystals. The crystals consist primarily of calcium phosphate in the form of hydroxyapatite, are located more frequently in the interstitial space of the renal papillae than intratubularly, particularly in older animals, and lack accompanying inflammatory cell infiltration. The interstitial deposits of hydroxyapatite observed in THP-null mice bear strong resemblances to the renal crystals found in human kidneys bearing idiopathic calcium oxalate stones. Compared with 24-h urine from the wild-type mice, that of THP-null mice is supersaturated with brushite (calcium phosphate), a stone precursor, and has reduced urinary excretion of citrate, a stone inhibitor. While less frequent than renal calcinosis, renal pelvic and ureteral stones and hydronephrosis occur in the aged THP-null mice. These results provide direct in vivo evidence indicating that normal THP plays an important role in defending the urinary system against calcification and suggest that reduced expression and/or decreased function of THP could contribute to nephrolithiasis.

  • renal calcinosis and stone formation in mice lacking osteopontin tamm horsfall Protein or both
    American Journal of Physiology-renal Physiology, 2007
    Co-Authors: Lucy Liaw, Andrew P Evan, Andre J Sommer, John C Lieske
    Abstract:

    Although often supersaturated with mineral salts such as calcium phosphate and calcium oxalate, normal urine possesses an innate ability to keep them from forming harmful crystals. This inhibitory ...

Xueru Wu - One of the best experts on this subject based on the ideXlab platform.

  • tamm horsfall Protein translocates to the basolateral domain of thick ascending limbs interstitium and circulation during recovery from acute kidney injury
    American Journal of Physiology-renal Physiology, 2013
    Co-Authors: Tarek M Elachkar, Ruth Mccracken, Monique R Heitmeier, Soline Bourgeois, Jan S Ryerse, Xueru Wu
    Abstract:

    Tamm-Horsfall Protein (THP) is a glycoProtein normally targeted to the apical membrane domain of the kidney's thick ascending limbs (TAL). We previously showed that THP of TAL confers protection to...

  • tamm horsfall Protein binds to type 1 fimbriated escherichia coli and prevents e coli from binding to uroplakin ia and ib receptors
    Journal of Biological Chemistry, 2001
    Co-Authors: Yongbing Pu, Zhongting Zhang, David L Hasty, Xueru Wu
    Abstract:

    Abstract The adherence of uropathogenic Escherichia coli to the urothelial surface, a critical first step in the pathogenesis of urinary tract infection (UTI), is controlled by three key elements: E. coli adhesins, host receptors, and host defense mechanisms. Although much has been learned about E. coli adhesins and their urothelial receptors, little is known about the role of host defense in the adherence process. Here we show that Tamm-Horsfall Protein (THP) is the principal urinary Protein that binds specifically to type 1 fimbriated E. coli, the main cause of UTI. The binding was highly specific and saturable and could be inhibited by d-mannose and abolished by endoglycosidase H treatment of THP, suggesting that the binding is mediated by the high-mannose moieties of THP. It is species-conserved, occurring in both human and mouse THPs. In addition, the binding to THP was much greater with an E. coli strain bearing a phenotypic variant of the type 1 fimbrial FimH adhesin characteristic of those prevalent in UTI isolates compared with the one prevalent in isolates from the large intestine of healthy individuals. Finally, a physiological concentration of THP completely abolished the binding of type 1 fimbriated E. coli to uroplakins Ia and Ib, two putative urothelial receptors for type 1 fimbriae. These results establish, on a functional level, that THP contains conserved high-mannose moieties capable of specific interaction with type 1 fimbriae and strongly suggest that this major urinary glycoProtein is a key urinary anti-adherence factor serving to prevent type 1 fimbriated E. coli from binding to the urothelial receptors.

Howard Trachtman - One of the best experts on this subject based on the ideXlab platform.

  • clinico pathologic findings in medullary cystic kidney disease type 2
    Pediatric Nephrology, 2005
    Co-Authors: Anthony J Bleyer, Thomas C Hart, Mark C Willingham, Samy S Iskandar, Michael C Gorry, Howard Trachtman
    Abstract:

    Medullary cystic kidney disease type 2 is an uncommon autosomal dominant condition characterized by juvenile onset hyperuricemia, precocious gout and chronic renal failure progressing to end-stage renal disease in the 4th through 7th decades of life. A family suffering from this condition is described. The patient in the index case presented with renal insufficiency as a child. A renal biopsy revealed tubular atrophy, and immunohistochemical staining of the tissue for uromodulin (Tamm Horsfall Protein) revealed dense deposits in renal tubular cells. Genetic testing revealed a single nucleotide mutation (c.899G>A) resulting in an exchange of a cysteine residue for tyrosine (C300Y). Medullary cystic kidney disease type 2 (also known as uromodulin-associated kidney disease) likely represents a form of endoplasmic reticulum storage disease, with deposition of the abnormal uromodulin Protein in the endoplasmic reticulum, leading to tubular cell atrophy and death.