Vitamin A Deficiency and Urinary Calcium Excretion in Rats

Zile, Maija H.; DeLuca, Hector F.; Ahrens, Helga

doi:10.1093/jn/102.10.1255

Cited by 10 publications

(5 citation statements)

References 15 publications

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“…It was recently reported that pkd1 gene, which is expressed in the collecting ducts, is a target gene of RA in vitro [25]; a DR1-type RARE was found in 5′-flanking region of aqp2 , a gene encoding the water channel aquaporin 2 expressed in the principal cells of collecting ducts [26]. We have also noted that post-natal vitamin A deficiency in experimental murine models has been correlated with a series of anomalies including dysregulation of urinary pH and metabolites, some of which are associated with an increased risk of developing urolithiasis [27]–[29], an altered structure and composition of the glomerular and tubular basement membrane [30], and alteration of cytokeratin expression in renal pelvic epithelium [31]. Whether the RA activity in the collecting ducts observed in this study is linked to the specialized functions of principal cells and intercalated cells, and whether it is linked to the regulation of the genes and abnormalities aforementioned, require further investigation.…”

Section: Discussionmentioning

confidence: 92%

Endogenous Retinoic Acid Activity in Principal Cells and Intercalated Cells of Mouse Collecting Duct System

Wong

Kopp

Roberts³

et al. 2011

PLoS ONE

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BackgroundRetinoic acid is the bioactive derivative of vitamin A, which plays an indispensible role in kidney development by activating retinoic acid receptors. Although the location, concentration and roles of endogenous retinoic acid in post-natal kidneys are poorly defined, there is accumulating evidence linking post-natal vitamin A deficiency to impaired renal concentrating and acidifying capacity associated with increased susceptibility to urolithiasis, renal inflammation and scarring. The aim of this study is to examine the presence and the detailed localization of endogenous retinoic acid activity in neonatal, young and adult mouse kidneys, to establish a fundamental ground for further research into potential target genes, as well as physiological and pathophysiological roles of endogenous retinoic acid in the post-natal kidneys.Methodology/Principal Findings RARE-hsp68-lacZ transgenic mice were employed as a reporter for endogenous retinoic acid activity that was determined by X-gal assay and immunostaining of the reporter gene product, β-galactosidase. Double immunostaining was performed for β-galactosidase and markers of kidney tubules to localize retinoic acid activity. Distinct pattern of retinoic acid activity was observed in kidneys, which is higher in neonatal and 1- to 3-week-old mice than that in 5- and 8-week-old mice. The activity was present specifically in the principal cells and the intercalated cells of the collecting duct system in all age groups, but was absent from the glomeruli, proximal tubules, thin limbs of Henle's loop and distal tubules.Conclusions/SignificanceEndogenous retinoic acid activity exists in principal cells and intercalated cells of the mouse collecting duct system after birth and persists into adulthood. This observation provides novel insights into potential roles for endogenous retinoic acid beyond nephrogenesis and warrants further studies to investigate target genes and functions of endogenous retinoic acid in the kidney after birth, particularly in the collecting duct system.

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Section: Discussionmentioning

confidence: 92%

Endogenous Retinoic Acid Activity in Principal Cells and Intercalated Cells of Mouse Collecting Duct System

Wong

Kopp

Roberts³

et al. 2011

PLoS ONE

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“…Dietary VA deficiency causes important changes in the composition of the urine with decreased pH, citrate, calcium, phosphate and glucosaminoglycans with regard to the pathogenesis of urinary calculi (Zile et al., 1972; Grases et al., 1998). Because of its inhibitory action on crystallization of insoluble salts, the decreased excretion of glucosaminoglycans has been considered to be an important risk factor for lesions of the renal and urothelial epithelium, and consequently, for the development of encrustations and calculogenesis (See and Williams, 1992).…”

Section: Discussionmentioning

confidence: 99%

Levels of Retinol and Retinyl Esters in Plasma and Urine of Dogs with Urolithiasis

Raila¹,

Forterre²,

Schweigert³

2003

Journal of Veterinary Medicine Series A

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Vitamin A (VA) deficiency and Tamm-Horsfall glycoprotein (THP), a protein that binds retinol and retinyl esters in canine urine, might be involved in the pathogenesis of urolithiasis in dogs. In the present study, we assessed levels of retinol, retinyl esters, retinol-binding protein (RBP) and THP in plasma and urine of dogs with a history of urolithiasis (n = 25) compared with clinically healthy controls (n = 18). Plasma retinol concentrations were higher in dogs with uroliths of struvit (P < 0.01), calcium oxalate (P < 0.05), urate (P < 0.01) and cysteine, but there were no differences in the concentrations of plasma RBP and retinyl esters. Excretion of urinary retinol and retinyl esters were tentatively, but not significantly higher in the stone-forming groups, which was accompanied by increased levels of urinary RBP (P < 0.01) and lower excretions in THP (P < 0.01). The results show that VA deficiency may be excluded as a potential cause for canine urolithiasis. However, the occurrence of RBP and a concomitant reduction of THP in urine indicates a disturbed kidney function as cause or consequence of stone formation in dogs.

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“…Moreover, post-natal vitamin A deficiency has been associated with renal anomalies, including increased incidence of pyelonephritis, kidney inflammation and fibrosis, polyuria and dysregulated urinary ion/solute content, urolithiasis, and delayed tissue repair [7], [41], [42], [43], [44]. Thus, the roles for the tRA/RAR target genes identified in this study in the aforementioned renal anomalies associated to post-natal vitamin A deficiency deserve further studies.…”

Section: Discussionmentioning

confidence: 64%

Retinoic Acid Receptor-Dependent, Cell-Autonomous, Endogenous Retinoic Acid Signaling and Its Target Genes in Mouse Collecting Duct Cells

et al. 2012

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BackgroundVitamin A is necessary for kidney development and has also been linked to regulation of solute and water homeostasis and to protection against kidney stone disease, infection, inflammation, and scarring. Most functions of vitamin A are mediated by its main active form, all-trans retinoic acid (tRA), which binds retinoic acid receptors (RARs) to modulate gene expression. We and others have recently reported that renal tRA/RAR activity is confined to the ureteric bud (UB) and collecting duct (CD) cell lineage, suggesting that endogenous tRA/RARs primarily act through regulating gene expression in these cells in embryonic and adult kidney, respectively.Methodology/Principal FindingsTo explore target genes of endogenous tRA/RARs, we employed the mIMCD-3 mouse inner medullary CD cell line, which is a model of CD principal cells and exhibits constitutive tRA/RAR activity as CD principal cells do in vivo. Combining antagonism of RARs, inhibition of tRA synthesis, exposure to exogenous tRA, and gene expression profiling techniques, we have identified 125 genes as candidate targets and validated 20 genes that were highly regulated (Dhrs3, Sprr1a, and Ppbp were the top three). Endogenous tRA/RARs were more important in maintaining, rather than suppressing, constitutive gene expression. Although many identified genes were expressed in UBs and/or CDs, their exact functions in this cell lineage are still poorly defined. Nevertheless, gene ontology analysis suggests that these genes are involved in kidney development, renal functioning, and regulation of tRA signaling.Conclusions/SignificanceA rigorous approach to defining target genes for endogenous tRA/RARs has been established. At the pan-genomic level, genes regulated by endogenous tRA/RARs in a CD cell line have been catalogued for the first time. Such a catalogue will guide further studies on molecular mediators of endogenous tRA/RARs during kidney development and in relation to renal defects associated with vitamin A deficiency.

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Vitamin A Deficiency and Urinary Calcium Excretion in Rats

Cited by 10 publications

References 15 publications

Endogenous Retinoic Acid Activity in Principal Cells and Intercalated Cells of Mouse Collecting Duct System

Endogenous Retinoic Acid Activity in Principal Cells and Intercalated Cells of Mouse Collecting Duct System

Levels of Retinol and Retinyl Esters in Plasma and Urine of Dogs with Urolithiasis

Retinoic Acid Receptor-Dependent, Cell-Autonomous, Endogenous Retinoic Acid Signaling and Its Target Genes in Mouse Collecting Duct Cells

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