Abnormal sulfate metabolism in vitamin D-deficient rats.

Fernandes, Isabelle; Hampson, Geeta; Cahours, Xavier; Morin, Pascal; Coureau, Christiane; Couette, Sylviane; Prié, Dominique; Biber, Jürg; Murer, Heini; Friedlander, Gérard; Silve, Caroline

doi:10.1172/jci119756

Cited by 59 publications

(46 citation statements)

References 33 publications

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“…However, vitamin D is also known to regulate RNA and protein levels of the anion transporter NaSi-1, important in the regulation of renal tubular sulfate reabsorption (7). In rats, 1,25D deficiency decreases plasma sulfate while increasing the fractional excretion of sulphate and these effects are normalized with 1,25D (35). We are not aware of any studies on direct effects of 1,25D on ammonium excretion.…”

Section: Discussionmentioning

confidence: 99%

Increased biological response to 1,25(OH)₂D₃in genetic hypercalciuric stone-forming rats

Frick

Asplin

Favus

et al. 2013

American Journal of Physiology-Renal Physiology

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Frick KK, Asplin JR, Favus MJ, Culbertson C, Krieger NS, Bushinsky DA. Increased biological response to 1,25(OH)2D3 in genetic hypercalciuric stone-forming rats. Am J Physiol Renal Physiol 304: F718-F726, 2013. First published January 23, 2013 doi:10.1152/ajprenal.00645.2012.-Genetic hypercalciuric stone-forming (GHS) rats, bred to maximize urine (U) calcium (Ca) excretion, have increased intestinal Ca absorption and bone Ca resorption and reduced renal Ca reabsorption, leading to increased UCa compared with the Sprague-Dawley (SD) rats. GHS rats have increased vitamin D receptors (VDR) at each of these sites, with normal levels of 1,25(OH)2D3 (1,25D), indicating that their VDR is undersaturated with 1,25D. We tested the hypothesis that 1,25D would induce a greater increase in UCa in GHS rats by feeding both strains ample Ca and injecting 1,25D (25 ng · 100 g body wt Ϫ1 · day Ϫ1 ) or vehicle for 16 days. With 1,25D, UCa in SD increased from 1.7 Ϯ 0.3 mg/day to 24.4 Ϯ 1.2 (⌬ ϭ 22.4 Ϯ 1.5) and increased more in GHS from 10.5 Ϯ 0.7 to 41.9 Ϯ 0.7 (⌬ ϭ 29.8 Ϯ 1.8; P ϭ 0.003). To determine the mechanism of the greater increase in UCa in GHS rats, we measured kidney RNA expression of components of renal Ca transport. Expression of transient receptor potential vanilloid (TRPV)5 and calbindin D28K were increased similarly in SD ϩ 1,25D and GHS ϩ 1,25D. The Na ϩ /Ca 2ϩ exchanger (NCX1) was increased in GHS ϩ 1,25D. Klotho was decreased in SD ϩ 1,25D and GHS ϩ 1,25D. TRPV6 was increased in SD ϩ 1,25D and increased further in GHS ϩ 1,25D. Claudin 14, 16, and 19, Na/K/2Cl transporter (NKCC2), and secretory K channel (ROMK) did not differ between SD ϩ 1,25D and GHS ϩ 1,25D. Increased UCa with 1,25D in GHS exceeded that of SD, indicating that the increased VDR in GHS induces a greater biological response. This increase in UCa, which must come from the intestine and/or bone, must exceed any effect of 1,25D on TRPV6 or NCX1-mediated renal Ca reabsorption. vitamin D; calcium; kidney stones; reabsorption HYPERCALCIURIA IS THE MOST common metabolic abnormality in patients with nephrolithiasis(19). Hypercalciuria leads to increased urine (U) supersaturation (SS) with respect to the solid phases of calcium hydrogen phosphate (CaHPO 4 , brushite) and calcium oxalate (CaOx), enhancing the probability of nucleation and growth of crystals into clinically significant stones (19). In humans, idiopathic hypercalciuria (IH) is characterized by increased intestinal calcium (Ca) absorption and/or decreased renal tubule Ca reabsorption resulting in hypercalciuria with normal serum (S) Ca, normal or elevated S1,25(OH) 2 D 3 (1,25D), normal S parathyroid hormone (PTH), normal or low S phosphate (P), and low bone mass (19,70,85). The familial pattern of IH is consistent with a polygenic mode of inheritance (70,71,85).To study the pathophysiology of hypercalciuria and stone formation, we have established a strain of hypercalciuric rats by selectively inbreeding Sprague-Dawley (SD) rats for increased UCa excretion (3-5, 16 -18, 20 -25, 27-29, 31, 3...

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Section: Discussionmentioning

confidence: 99%

Increased biological response to 1,25(OH)₂D₃in genetic hypercalciuric stone-forming rats

Frick

Asplin

Favus

et al. 2013

American Journal of Physiology-Renal Physiology

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“…This cotransporter is predominantly expressed in the kidney cortex and ileum and contains two mRNA species of 2.3 and 2.9 kb. Previous studies show that thyroid hormone, glucocorticoids, and vitamin D can modulate serum sulfate levels, renal sulfate handling, and NaSi-1 expression (14,35,41). Vitamin D deficiency in rats leads to lower serum sulfate levels and decreased NaSi-1 expression (14), but sulfate metabolism in vitamin D receptor (VDR)-deficient animals has not been reported.…”

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confidence: 98%

“…Previous studies show that thyroid hormone, glucocorticoids, and vitamin D can modulate serum sulfate levels, renal sulfate handling, and NaSi-1 expression (14,35,41). Vitamin D deficiency in rats leads to lower serum sulfate levels and decreased NaSi-1 expression (14), but sulfate metabolism in vitamin D receptor (VDR)-deficient animals has not been reported. In the present study, we used VDR knockout mice as a model to further investigate the role of vitamin D in sulfate homeostasis.…”

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confidence: 98%

Critical role of vitamin D in sulfate homeostasis: regulation of the sodium-sulfate cotransporter by 1,25-dihydroxyvitamin D₃

Bolt¹,

Liu²,

Qiao³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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Critical role of vitamin D in sulfate homeostasis: regulation of the sodium-sulfate cotransporter by 1,25-dihydroxyvitamin D3. Am J Physiol Endocrinol Metab 287: E744 -E749, 2004. First published May 27, 2004 10.1152/ajpendo.00151.2004.-As the fourth most abundant anion in the body, sulfate plays an essential role in numerous physiological processes. One key protein involved in transcellular transport of sulfate is the sodium-sulfate cotransporter NaSi-1, and previous studies suggest that vitamin D modulates sulfate homeostasis by regulating NaSi-1 expression. In the present study, we found that, in mice lacking the vitamin D receptor (VDR), NaSi-1 expression in the kidney was reduced by 72% but intestinal NaSi-1 levels remained unchanged. In connection with these findings, urinary sulfate excretion was increased by 42% whereas serum sulfate concentration was reduced by 50% in VDR knockout mice. Moreover, levels of hepatic glutathione and skeletal sulfated proteoglycans were also reduced by 18 and 45%, respectively, in the mutant mice. Similar results were observed in VDR knockout mice after their blood ionized calcium levels and rachitic bone phenotype were normalized by dietary means, indicating that vitamin D regulation of NaSi-1 expression and sulfate metabolism is independent of its role in calcium metabolism. Treatment of wild-type mice with 1,25-dihydroxyvitamin D3 or vitamin D analog markedly stimulated renal NaSi-1 mRNA expression. These data provide strong in vivo evidence that vitamin D plays a critical role in sulfate homeostasis. However, the observation that serum sulfate and skeletal proteoglycan levels in normocalcemic VDR knockout mice remained low in the absence of rickets and osteomalacia suggests that the contribution of sulfate deficiency to development of rickets and osteomalacia is minimal.vitamin D receptor; sulfate INORGANIC SULFATE is the fourth most abundant anion in mammalian plasma. As such, sulfate is essential for numerous physiological functions. For instance, sulfate is involved in activation and detoxification of a variety of endogenous and exogenous substances such as xenobiotics, steroids, neurotransmitters, and bile acids (30, 31). Sulfate conjugation is essential for biosynthesis of a large number of structural proteins such as sulfated glycosaminoglycans (a major component of the cartilage), cerebroside sulfate (a constituent of the myelin membranes in the brain), and heparin sulfate (required for anticoagulation) (10,12,32). Undersulfation of cartilage proteoglycans has been linked to three types of human inherited osteochondrodysplasia disorders, which are caused by mutations in the diastrophic dysplasia sulfate transporter gene (17,18,39,40). Diastrophic dysplasia sulfate transporter protein transports extracellular sulfate into chondrocytes.In mammals, sulfate homeostasis is largely regulated by the kidney. The majority of filtered sulfate is reabsorbed in the proximal tubules, and only ϳ5-20% of the filtered load is excreted into the urine (5, 29). Transcellular trans...

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“…It is currently believed that the presence of Vascular endothelial growth factor (VEGF) in IVDs originates from inflammatory chain (IL-1β and TNF-α in the NP) due to metabolic requirement of the region [22].…”

Section: Vitamin D Receptor (Vdr)mentioning

confidence: 99%

Etiology and Risk Factors of Lumbar Intervertebral Disc (IVD) Degeneration

Debnath¹

2018

RMES

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Biological factors (Table 1) Changes in ECM (Extracellular Matrix): Collagen synthesis increases in the initial stages of degeneration with a clear increase in type II Collagen in the NP (maybe indicating repair mechanism) [9]. As the degeneration progresses the synthesis pattern changes and more type II Collagen is synthesized in AF. Type I collagen is synthesized in the deep region of AF and NP. Type X collagen formation is associated with chondrocyte agglomerates and tears of degenerated IVDs. The synthesis of proteoglycans also changes with decline in production of aggrecan and increase in the synthesis of versican, biglycan and decorin. There is reduced Glycosaminoglycans (GAGs) esp. modification of chondroitin sulfate to keratan sulfate. These results in disc desiccation and degeneration [10]. The remodeling of the ECM results from these changes occurring simultaneously. The protagonists of the process are the matrix metallo-proteinases (MMPs) [11]. There are ADAMTS (a desintegrin and metalloproteinase with thrombospondin), which play similar but more powerful roles like MMPs. Both these families have the same endogenous inhibitors called TIMPs (Tissue inhibitor matrix metallo-proteinases), which act synergistically in the remodeling of ECM [12]. Review Article Research in Medical & Engineering Sciences C CRIMSON PUBLISHERS Wings to the Research 1/10Copyright © All rights are reserved by Ujjwal K Debnath. Volume 4 -Issue 5 ISSN: 2576-8816 AbstractLumbar degenerative disc disease (DDD) is a progressive condition that exists along a continuum of pathologic processes. The disease starts as desiccation of the nucleus pulposus, to annular tearing, diffuse disc bulging, and disc space collapse, the degenerative process can occur over the course of decades, culminating in substantial debilitation. Clinically DDD presents with back pain and/or radiculopathy, can limit work and productivity. Additionally, the cost of treating this condition is especially high, and billions of dollars are spent on managing degenerative spinal processes annually.In this review, the main focus is on the recent advances in studies on the most extensively examined risk factors and genetic factors associated with DDD in humans. A number of genetic defects have been correlated with structural and functional changes within the intervertebral disc (IVD), which may compromise the disc's mechanical properties and metabolic activities. These studies have begun to shed light on the molecular basis of DDD, suggesting that genetic factors are important contributors to the onset and progression of IDD. By continuing to improve our understanding of the molecular mechanisms of DDD, specific early diagnosis and more effective treatments for this disabling disease may be possible in the future. Res Med Eng Sci 2/10How Proinflammatory cytokinesMost important cytokines which influences the IVD degeneration process are Interleukin -1 (IL-1) and Tumor necrosis factor-α (TNF-α). Large volumes of research and evidence suggest these cytokines are directly ...

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Abnormal sulfate metabolism in vitamin D-deficient rats.

Abstract: To explore the possibility that vitamin D status regulates sulfate homeostasis, plasma sulfate levels, renal sulfate excretion, and the expression of the renal Na-SO 4

Cited by 59 publications

References 33 publications

Increased biological response to 1,25(OH)₂D₃in genetic hypercalciuric stone-forming rats

Increased biological response to 1,25(OH)₂D₃in genetic hypercalciuric stone-forming rats

Critical role of vitamin D in sulfate homeostasis: regulation of the sodium-sulfate cotransporter by 1,25-dihydroxyvitamin D₃

Etiology and Risk Factors of Lumbar Intervertebral Disc (IVD) Degeneration

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Abnormal sulfate metabolism in vitamin D-deficient rats.

Abstract: To explore the possibility that vitamin D status regulates sulfate homeostasis, plasma sulfate levels, renal sulfate excretion, and the expression of the renal Na-SO 4

Cited by 59 publications

References 33 publications

Increased biological response to 1,25(OH)2D3in genetic hypercalciuric stone-forming rats

Increased biological response to 1,25(OH)2D3in genetic hypercalciuric stone-forming rats

Critical role of vitamin D in sulfate homeostasis: regulation of the sodium-sulfate cotransporter by 1,25-dihydroxyvitamin D3

Etiology and Risk Factors of Lumbar Intervertebral Disc (IVD) Degeneration

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Increased biological response to 1,25(OH)₂D₃in genetic hypercalciuric stone-forming rats

Increased biological response to 1,25(OH)₂D₃in genetic hypercalciuric stone-forming rats

Critical role of vitamin D in sulfate homeostasis: regulation of the sodium-sulfate cotransporter by 1,25-dihydroxyvitamin D₃