Ontogeny of renal phosphate transport and the process of growth

Spitzer, Adrian; Barac‐Nieto, Mario

doi:10.1007/s004670100629

Cited by 39 publications

(24 citation statements)

References 56 publications

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“…In addition, a specific type IIa-related Na/P i cotransporter protein was postulated to account for high P i transport rates in weaning animals (7). Evidence for this was obtained by antisense experiments and transport expression in Xenopus oocytes (1,7). When mRNA isolated from the kidney cortex of rapidly growing rats was treated with type IIa transporter antisense oligonucleotides or was depleted of type IIa-specific mRNA by a subtractive hybridization procedure, Na ϩ -dependent P i uptake was still detected in injected oocytes (1,7).…”

mentioning

confidence: 93%

“…Evidence for this was obtained by antisense experiments and transport expression in Xenopus oocytes (1,7). When mRNA isolated from the kidney cortex of rapidly growing rats was treated with type IIa transporter antisense oligonucleotides or was depleted of type IIa-specific mRNA by a subtractive hybridization procedure, Na ϩ -dependent P i uptake was still detected in injected oocytes (1,7). The type IIa transporter-depleted mRNA contained a mRNA species that showed some sequence homology to the type IIa transporter encoding message.…”

mentioning

confidence: 94%

“…Immunoblotting Analysis-Brush-border membrane vesicles (BBMVs) 1 were prepared from rat kidney by the Ca 2ϩ precipitation method as described previously (14). The levels of leucine aminopeptidase, Na ϩ K ϩ -ATPase, and cytochrome c oxidase were measured to assess the purity of the membranes.…”

Section: Antisense Hybrid Depletion-for Hybrid Depletion Experimentsmentioning

confidence: 99%

“…The kidneys contribute to the maintenance of the positive P i balance required for growth by reabsorbing a high fraction of the filtered P i (1). The capacity for Na ϩ -dependent phosphate cotransport across the luminal brush border membrane of renal proximal tubular cells is higher in juveniles than in adults (2,3).…”

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confidence: 99%

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Growth-related Renal Type II Na/Pi Cotransporter

Segawa

Kaneko

Takahashi

et al. 2002

Journal of Biological Chemistry

279

348

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Growth is critically dependent on the retention of a variety of nutrients. The kidney contributes to this positive external balance. In the present study, we isolated a cDNA from the human and rat kidney that encodes a growth-related Na ؉ -dependent inorganic phosphate (P i ) cotransporter (type IIc). Microinjection of type IIc cRNA into Xenopus oocytes demonstrated sodium-dependent P i cotransport activity. Affinity for P i was 0.07 mM in 100 mM Na ؉ . The transport activity was dependent on extracellular pH. In electrophysiological studies, type IIc Na/P i cotransport was electroneutral, whereas type IIa was highly electrogenic. In Northern blotting analysis, the type IIc transcript was only expressed in the kidney and highly in weaning animals. In immunohistochemical analysis, the type IIc protein was shown to be localized at the apical membrane of the proximal tubular cells in superficial and midcortical nephrons of weaning rat kidney. Hybrid depletion experiments suggested that type IIc could function as a Na/P i cotransporter in weaning animals, but its role is reduced in adults. The finding of the present study suggest that the type IIc is a growth-related renal Na/P i cotransporter, which has a high affinity for P i and is electroneutral.

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confidence: 93%

mentioning

confidence: 94%

Section: Antisense Hybrid Depletion-for Hybrid Depletion Experimentsmentioning

confidence: 99%

mentioning

confidence: 99%

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Growth-related Renal Type II Na/Pi Cotransporter

Segawa

Kaneko

Takahashi

et al. 2002

Journal of Biological Chemistry

279

348

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“…The kidneys regulate the excretion of P i in response to varying intake, by adjusting the relationship between filtered load and tubular reabsorption (25). In turn, tubular reabsorption of phosphate is mediated by a family of luminal and basolateral phosphate transporters, which can be divided into three overall groups (I-III), all of which have members that are expressed in the renal cortex.…”

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confidence: 99%

A murine transgenic model for transcriptional regulation of the Na/Pi-IIa major renal phosphate cotransporter

Rosenberg¹,

Shachaf²,

Tzukerman³

et al. 2007

American Journal of Physiology-Renal Physiology

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Rosenberg T, Shachaf C, Tzukerman M, Skorecki K. A murine transgenic model for transcriptional regulation of the Na/ Pi-IIa major renal phosphate cotransporter. Am J Physiol Renal Physiol 292: F1617-F1625, 2007. First published February 6, 2007; doi:10.1152/ajprenal.00412.2006.-Levels of the type IIa Na/P i (Na/Pi-IIa) cotransporter, which serves as the principal mediator of phosphate reabsorption in the kidney, can be modulated through posttranscriptional or posttranslational mechanisms by dietary, hormonal, and pharmacological influences. Previous studies have not demonstrated clear-cut evidence for modulation of Na/Pi-IIa cotransporter levels through transcriptional mechanisms. We have previously demonstrated that a 4.7-kb rat genomic fragment upstream of the rodent Npt2 gene encoding the Na/Pi-IIa cotransporter, is sufficient to mediate its transcriptional activity in vitro (Shachaf C, Skorecki KL, Tzukerman M. Am J Physiol Renal Physiol 278: F406 -F416, 2000). Accordingly, we have established an in vivo experimental model in which this Npt2 genomic fragment fused upstream of a Lac Z reporter gene was expressed as a transgene in mice. The nine independent transgenic founder lines generated exhibited Lac Z reporter gene expression specifically in the renal cortex. This renal cortical-specific expression driven by the Npt2 promoter was confirmed at the mRNA and protein levels using RT-PCR, histochemistry, and Lac Z enzymatic activity. Furthermore, the expression of the transgene correlated with expression of the endogenous Npt2 gene during embryonic and early postnatal development. Thus we have generated a transgenic mouse model which will enable in vivo investigation of the contribution of transcriptional mechanisms to the overall regulation of Na/Pi-IIa expression under physiological and pathophysiological conditions. Npt2; Lac ZINORGANIC PHOSPHATE (P i ) is of critical importance to cellular function, as well to development of the skeletal system, especially during periods of growth (21). The kidneys regulate the excretion of P i in response to varying intake, by adjusting the relationship between filtered load and tubular reabsorption (25). In turn, tubular reabsorption of phosphate is mediated by a family of luminal and basolateral phosphate transporters, which can be divided into three overall groups (I-III), all of which have members that are expressed in the renal cortex. The family of type II sodium-dependant phosphate cotransporters include the type IIa and IIc transporters, expressed on the luminal membrane of the proximal tubule of the kidney, and the type IIb transporter, expressed in the lung and small intestine. Functional studies, including murine knockout models, indicate that the Na/Pi-IIa cotransporter mediates at least 70% of tubular reabsorption of phosphate in the mature kidney and is rate limiting for overall renal phosphate reabsorption (for a review, see Ref. 14 and references therein). Residual phosphate reabsorption across the luminal membrane is mediated by the Na/Pi-IIc cotranspo...

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Disorders of Phosphorus Homeostasis

Johnson

2009

Fluid and Electrolytes in Pediatrics

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Ontogeny of renal phosphate transport and the process of growth

Cited by 39 publications

References 56 publications

Growth-related Renal Type II Na/Pi Cotransporter

Growth-related Renal Type II Na/Pi Cotransporter

A murine transgenic model for transcriptional regulation of the Na/Pi-IIa major renal phosphate cotransporter

Disorders of Phosphorus Homeostasis

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