Calcium oxalate monohydrate aggregation induced by aggregation of desialylated Tamm-Horsfall protein

Viswanathan, Pragasam; Rimer, Jeffrey D.; Kolbach, Ann M.; Ward, Michael D.; Kleinman, Joel C.; Wesson, Jeffrey A.

doi:10.1007/s00240-010-0353-7

Cited by 60 publications

(68 citation statements)

References 63 publications

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“…Unless more reproducible sample preparation, storage and quantitation methodologies become a gold standard for different laboratories, such as the one recently published [77], it would be premature and misleading to conclude that quantitative defects of THP do not exist in stone formers. Finally, qualitative deficiencies such as insufficient sialylation of THP have been suggested to cause a functional defect in the inhibition of stone formation [40, 54, 78, 79]. These human-relevant topics are undoubtedly worthy of further exploration.…”

Section: Tamm-horsfall Protein Knockout Micementioning

confidence: 99%

Interstitial calcinosis in renal papillae of genetically engineered mouse models: relation to Randall’s plaques

2014

Urolithiasis

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Genetically engineered mouse models (GEMMs) have been highly instrumental in elucidating gene functions and molecular pathogenesis of human diseases, although their use in studying kidney stone formation or nephrolithiasis remains relatively limited. This review intends to provide an overview of several knockout mouse models that develop interstitial calcinosis in the renal papillae. Included herein are mice deficient for Tamm-Horsfall protein (THP; also named uromodulin), osteopontin (OPN), both THP and OPN, Na+-phosphate cotransporter Type II (Npt2a) and Na+/H+ exchanger regulatory factor (NHERF-1). The baseline information of each protein is summarized, along with key morphological features of the interstitial calcium deposits in mice lacking these proteins. Attempts are made to correlate the papillary interstitial deposits found in GEMMs with Randall’s plaques, the latter considered precursors of idiopathic calcium stones in patients. The pathophysiology that underlies the renal calcinosis in the knockout mice are also discussed wherever information is available. Not all the knockout models are allocated equal space because some are more extensively characterized than others. Despite the inroads already made, the exact physiological underpinning, origin, evolution and fate of the papillary interstitial calcinosis in the GEMMs remain incompletely defined. Greater investigative efforts are warranted in order to pin down the precise role of the papillary interstitial calcinosis in nephrolithiasis using the existing models. Additionally, more sophisticated, second-generation GEMMs that allow gene inactivation in a time-controlled manner and “compound mice” that bear several genetic alterations are urgently needed, in light of mounting evidence that nephrolithiasis is a multifactorial, multi-stage and polygenic disease.

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Section: Tamm-horsfall Protein Knockout Micementioning

confidence: 99%

Interstitial calcinosis in renal papillae of genetically engineered mouse models: relation to Randall’s plaques

2014

Urolithiasis

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“…An insufficient crystal coating and electrostatic repulsion was therefore suggested to be responsible for AGN and stone formation. On the other hand it was shown that desialylation of Tamm Horsfall glycoprotein (THG) provoked self AGN of THG and AGN of CaOx crystals [49] , effects which were also demonstrated in experiments performed with albumin (Figures 8 and 9). Desialylation reduces anionic domains and thus reinforces hydrophobic groups of THG being responsible for hydrophobic protein binding.…”

mentioning

confidence: 69%

“…The inhibition of crystallization processes by UM's is mainly attributed to anionic residues like carboxyglutamic acid [44,45] , phosphate [46,47] and sialic acid [48,49] which have a high affinity to the Ca of crystals. Some of these anionic groups being responsible for the electro-negative charge of coated crystals were found to be reduced in UM's of stone patients.…”

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confidence: 99%

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From crystalluria to kidney stones, some physicochemical aspects of calcium nephrolithiasis

Baumann¹,

Affolter²

2014

WJN

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Nephrolithiasis seems to be the result of crystal formation, aggregation and retention in the kidney during crystalluria. These processes have to occur within the short urinary transit time through the kidney being in the order of few minutes. Recently much work was done on rather qualitative aspects of nephrolithiasis like genetics, metabolism and morphology. In this review we try to provide some quantitative information on urinary supersaturation with respect to stone minerals, especially Ca oxalate (CaOx), on the formation and aggregation of CaOx crystals and on crystal retention in the kidney. The paper is centered on idiopathic Ca nephrolithiasis being the most frequent stone disease with only partially known pathogenesis. New aspects of the role of urinary macromolecules in stone formation and of the mechanism of crystal aggregation are provided.

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“…In fact, RP as well as the stones themselves contain various amounts of proteins and polysaccharides, including albumin, globulin, Tamm-Horsfall glycoprotein (THP), prothrombin fragment 1, inter-a-trypsin inhibitor (bikunin), osteopontin (OPN), and calprotectin, all of which could conceivably contribute to forming an amorphous phase, or even a PILP-like phase, as demonstrated for various acidic polymers in our group [66–68]. These components are termed crystal matrix proteins, and constitute 1 5% of RP and urinary stones, implying that they may have some influence in the stone-formation process [10, 31, 34, 36, 38, 39, 41, 50, 51, 55, 69–71]. …”

Section: Introductionmentioning

confidence: 87%

Biomimetic Randall’s plaque as an in vitro model system for studying the role of acidic biopolymers in idiopathic stone formation

et al. 2014

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Randall’s plaque (RP) deposits seem to be consistent among the most common type of kidney stone formers, idiopathic calcium oxalate stone formers. This group forms calcium oxalate renal stones without any systemic symptoms, which contributes to the difficulty of understanding and treating this painful and recurring disease. Thus, the development of an in vitro model system to study idiopathic nephrolithiasis, beginning with RP pathogenesis, can help in identifying how plaques, and subsequently stones, form. One main theory of RP formation is that calcium phosphate deposits initially form in the basement membrane of the thin loops of Henle, which then fuse and spread into the interstitial tissue, and ultimately make their way across the urothelium, where upon exposure to the urine, the mineralized tissue serves as a nidus for overgrowth with calcium oxalate into a stone. Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically-laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid-precursor (PILP) process, in which acidic polypeptides induce a liquid-phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. Given that there are many acidic proteins and polysaccharides present in the renal tissue and urine, we have put for the hypothesis that the PILP system may be involved in urolithiasis. Therefore, our goal is to develop an in vitro model system of these two stages of composite stone formation in order to study the role that various acidic macromolecules may play. In our initial experiments presented here, the development of “biomimetic” RP was investigated, which will then serve as a nidus for calcium oxalate overgrowth studies. In order to mimic the tissue environment, MatriStem® (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. We found that when using the PILP process to mineralize this tissue matrix, the two sides led to dramatically different mineral textures, and they bore a striking resemblance to native RP, which was not seen in the tissue mineralized via the classical crystal nucleation and growth process. The interstitium side predominantly consisted of collagen associated mineral, while the luminal side had much less mineral, which appeared to be tiny spherules embedded within the basement membrane. Although these studies are only preliminary, they support our hypothesis that kidney stones may involve non-classical crystallization pathways induced by the large variety of macromolecular species in the urinary environment. We believe that mineralization of native tissue scaffolds is useful for developing a model system of stone formation, with the ultimate goal of developing strategies to avoid RP and its detrimental consequences i...

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Calcium oxalate monohydrate aggregation induced by aggregation of desialylated Tamm-Horsfall protein

Cited by 60 publications

References 63 publications

Interstitial calcinosis in renal papillae of genetically engineered mouse models: relation to Randall’s plaques

Interstitial calcinosis in renal papillae of genetically engineered mouse models: relation to Randall’s plaques

From crystalluria to kidney stones, some physicochemical aspects of calcium nephrolithiasis

Biomimetic Randall’s plaque as an in vitro model system for studying the role of acidic biopolymers in idiopathic stone formation

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