Decreased Renal Expression of the Putative Calcium Oxalate Inhibitor Tamm-Horsfall Protein in the Ethylene Glycol Rat Model of Calcium Oxalate Urolithiasis.

Marengo, Susan Ruth; Chen, Daniel H.-C.; Kaung, Hue Lee C; Resnick, Martin I.; Lei, Yang

doi:10.1016/s0022-5347(05)65127-0

Cited by 38 publications

(15 citation statements)

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“…Other studies have, however, shown either a decrease 45 or an increase 46 in THP expression and production. Production and urinary excretion of OPN, 30,42 PT, 43 various ITI-related proteins, 31,32 and HS 44 is substantially increased as determined by detection of their specific mRNAs using in situ hybridization, reverse transcription polymerase chain reaction, or both.…”

Section: Animal Model Studiesmentioning

confidence: 82%

Crystal-induced inflammation of the kidneys: results from human studies, animal models, and tissue-culture studies

2004

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Calcium oxalate (CaOx), calcium phosphate (CaP), and uric acid or urate are the most common crystals seen in the kidneys. Most of the crystals evoke an inflammatory response leading to fibrosis, loss of nephrons, and eventually to chronic renal failure. Of the three, CaOx monohydrate is the most reactive, whereas some forms of CaP do not evoke any discernible response. Reactive oxygen species are produced during the interactions between the crystals and renal cells and are responsible for the various cellular responses. CaOx crystals generally form in the renal tubules. Exposure of renal epithelial cells to CaOx crystals results in the increased synthesis of osteopontin, bikunin, heparan sulfate, monocyte chemoattractant protein 1 (MCP-1), and prostaglandin (PG) E2, which are known to participate in inflammatory processes and in extracellular matrix production. CaOx crystal deposition in rat kidneys also activates the renin-angiotensin system. Both Ox and CaOx crystals selectively activate p38 mitogen-activated protein kinase (MAPK) in exposed tubular cells. CaP crystals can form in the tubular lumen, tubular cells, or tubular basement membrane. Renal epithelial cells exposed to brushite crystals produce MCP-1. Basic CaP and calcium pyrophosphate dihydrate induce mitogenesis in fibroblasts, stimulate production of PGE2, and up-regulate the synthesis of metalloproteinases (MMP) while down-regulating the production of inhibitors of MMPs through activation of p42/44 MAPK. Deposition of urate crystals in the kidneys becomes associated with renal tubular atrophy, interstitial fibrosis, and development of inflammatory infiltrate. Renal epithelial cells exposed to uric acid crystals synthesize MCP-1 as well as PGE2. Monocytes or neutrophils exposed to urate crystals produce tumor necrosis factor alpha, interleukin-1 (IL-1), IL-6, and IL-8. Expression of IL-8 is mediated through extracellular signal-regulated kinase 1 (ERK-1)/ERK-2 and nuclear transcription factors activated protein 1 and nuclear factor kappabeta. Urate crystals also stimulate the macrophages to produce MMPs.

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Section: Animal Model Studiesmentioning

confidence: 82%

Crystal-induced inflammation of the kidneys: results from human studies, animal models, and tissue-culture studies

2004

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“…Multiple published studies have clearly shown that a set of specific proteins are differentially-expressed in the kidneys of rats in response to treatments that induce a state of hyperoxaluria [30], [37]–[44]. These proteins include Osteopontin (encoded by Opn ), Mcp-1 (encoded by Ccl2 ), and Matrix-Gla protein (encoded by Mgp ) which tend to be up-regulated, and the inhibitor Tamm-Horsfall protein (encoded by Thp ) that appears to be down-regulated [44].…”

Section: Resultsmentioning

confidence: 99%

“…These proteins include Osteopontin (encoded by Opn ), Mcp-1 (encoded by Ccl2 ), and Matrix-Gla protein (encoded by Mgp ) which tend to be up-regulated, and the inhibitor Tamm-Horsfall protein (encoded by Thp ) that appears to be down-regulated [44]. In the current study, and presented in Figure 6, the genes for these four proteins are also differentially-expressed in both renal cortex and medulla tissues of HLP-fed rats, with Opn, Ccl2 and Mgp each up-regulated and Thp down-regulated, as would be predicted from our previous results (28).…”

Section: Resultsmentioning

confidence: 99%

Apocynin-Treatment Reverses Hyperoxaluria Induced Changes in NADPH Oxidase System Expression in Rat Kidneys: A Transcriptional Study

et al. 2012

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PurposeWe have previously shown that production of reactive oxygen species (ROS) is an important contributor to renal injury and inflammation following exposure to oxalate (Ox) or calcium-oxalate (CaOx) crystals. The present study was conducted, utilizing global transcriptome analyses, to determine the effect of Apocynin on changes in the NADPH oxidase system activated in kidneys of rats fed a diet leading to hyperoxaluria and CaOx crystal deposition.ApproachAge-, sex- and weight-matched rats were either fed regular rat chow or regular rat chow supplemented with 5% w/w hydroxy-L-proline (HLP). Half of the rats on the HLP diet were also placed on Apocynin-supplemented H2O. After 28 days, each rat was euthanized, their kidneys freshly explanted and dissected to obtain both cortex and medulla tissues. Total RNA was extracted from each tissue and subjected to genomic microarrays to obtain global transcriptome data. KEGG was used to identify gene clusters with differentially expressed genes. Immunohistochemistry was used to confirm protein expressions of selected genes.ResultsGenes encoding both membrane- and cytosolic-NADPH oxidase complex-associated proteins, together with p21rac and Rap1a, were coordinately up-regulated significantly in both renal medulla and cortex tissues in the HLP-fed rats compared to normal healthy untreated controls. Activation of NADPH oxidase appears to occur via the angiotensin-II/angiotensin-II receptor-2 pathway, although the DAG-PKC pathway of neutrophils may also contribute. Immuno histochemical staining confirmed up-regulated gene expressions. Simultaneously, genes encoding ROS scavenger proteins were down-regulated. HLP-fed rats receiving Apocynin had a complete reversal in the differential-expression of the NADPH oxidase system genes, despite showing similar levels of hyperoxaluria.ConclusionsA strong up-regulation of an oxidative/respiratory burst involving the NADPH oxidase system, activated via the angiotensin-II and most likely the DAG-PKC pathways, occurs in kidneys of hyperoxaluric rats. Apocynin treatment reversed this activation without affecting the levels of hyperoxaluria.

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“…92 The exposure of renal epithelial cells to oxalate causes oxidative damage, mitochondrial damage, activation of second messenger path ways (such as those mediated by p38 MAP kinase and phospholipase A), inflammatory response signaling, changes in the expression of putative modulators of crystallization (such as osteopontin, bikunin and Tamm-Horsfall protein), and changes in the glycocalyx. [93][94][95][96][97][98][99][100][101][102][103][104] The effects of oxalate on renal epithelial cells have been extensively discussed by Jonassen et al 105 Although some of these effects are directly due to oxalate, others are secondary to oxalate induced oxidative damage or inflammatory responses. 96,106 The changes effected by oxalate could promote nephrolithiasis by providing debris for crystal nucleation, making the apical plasma membrane more adhesive to crystals, or altering the availability of crystallizationinhibiting proteins.…”

Section: Potential Roles Of Oxalate In Nephrolithiasismentioning

confidence: 99%

Oxalate in renal stone disease: the terminal metabolite that just won't go away

Marengo

Romani

2008

Nat Rev Nephrol

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The incidence of calcium oxalate nephrolithiasis in the US has been increasing throughout the past three decades. Biopsy studies show that both calcium oxalate nephrolithiasis and nephrocalcinosis probably occur by different mechanisms in different subsets of patients. Before more-effective medical therapies can be developed for these conditions, we must understand the mechanisms governing the transport and excretion of oxalate and the interactions of the ion in general and renal physiology. Blood oxalate derives from diet, degradation of ascorbate, and production by the liver and erythrocytes. In mammals, oxalate is a terminal metabolite that must be excreted or sequestered. The kidneys are the primary route of excretion and the site of oxalate's only known function. Oxalate stimulates the uptake of chloride, water, and sodium by the proximal tubule through the exchange of oxalate for sulfate or chloride via the solute carrier SLC26A6. Fecal excretion of oxalate is stimulated by hyperoxalemia in rodents, but no similar phenomenon has been observed in humans. Studies in which rats were treated with (14)C-oxalate have shown that less than 2% of a chronic oxalate load accumulates in the internal organs, plasma, and skeleton. These studies have also demonstrated that there is interindividual variability in the accumulation of oxalate, especially by the kidney. This Review summarizes the transport and function of oxalate in mammalian physiology and the ion's potential roles in nephrolithiasis and nephrocalcinosis.

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Decreased Renal Expression of the Putative Calcium Oxalate Inhibitor Tamm-Horsfall Protein in the Ethylene Glycol Rat Model of Calcium Oxalate Urolithiasis.

Cited by 38 publications

References 25 publications

Crystal-induced inflammation of the kidneys: results from human studies, animal models, and tissue-culture studies

Crystal-induced inflammation of the kidneys: results from human studies, animal models, and tissue-culture studies

Apocynin-Treatment Reverses Hyperoxaluria Induced Changes in NADPH Oxidase System Expression in Rat Kidneys: A Transcriptional Study

Oxalate in renal stone disease: the terminal metabolite that just won't go away

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