Departments of Pediatrics and Physiology, Steele Memorial Children's Research Center, University of Arizona Health Sciences Center, Tucson, Arizona 85724
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ABSTRACT |
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The current studies were designed to characterize type IIb sodium-inorganic phosphate (Pi) cotransporter (NaPi-IIb) expression and to assess the effect of 1,25-(OH)2 vitamin D3 on NaPi-IIb gene expression during rat ontogeny. Sodium-dependent Pi absorption by intestinal brush-border membrane vesicles (BBMVs) decreased with age, and NaPi-IIb gene expression also decreased proportionally with age. 1,25-(OH)2 vitamin D3 treatment increased intestinal BBMV Pi absorption by ~2.5-fold in suckling rats and by ~2.1-fold in adult rats. 1,25-(OH)2 vitamin D3 treatment also increased NaPi-IIb mRNA abundance by ~2-fold in 14-day-old rats but had no effect on mRNA expression in adults. Furthermore, in rat intestinal epithelial (RIE) cells, 1,25-(OH)2 vitamin D3 increased NaPi-IIb mRNA abundance, an effect that was abolished by actinomycin D. Additionally, human NaPi-IIb gene promoter activity in transiently transfected RIE cells showed ~1.6-fold increase after 1,25-(OH)2 vitamin D3 treatment. In conclusion, we demonstrate that the age-related decrease in intestinal sodium-dependent Pi absorption correlates with decreased NaPi-IIb mRNA expression. Our data also suggest that the effect of 1,25-(OH)2 vitamin D3 on NaPi-IIb expression is at least partially mediated by gene transcription in suckling rats.
gene regulation; rat intestinal epithelial cells; ontogeny
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INTRODUCTION |
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INORGANIC PHOSPHATE (Pi) plays important roles in growth, development, bone formation, acid-base regulation, and cellular metabolism. The rate of growth is limited by the availability of Pi. A transport system capable of accumulating Pi against the electrochemical gradient is vital for normal development. The sodium-phosphate (NaPi) cotransporters are plasma membrane-bound symporters that mediate the movement of extracellular Pi ions into cells coupled with sodium ions. Three families of NaPi cotransporters have been identified from mammalian cells in recent years, called types I, II, and III (35, 53, 54). These proteins play important roles in regulating phosphate absorption across cell membranes and in maintaining serum Pi levels.
The small intestine is an important site for phosphate absorption. Early studies showed that Pi transport through the apical membrane of small intestinal epithelial cells is coupled with sodium (4, 7, 12, 21, 29, 43, 47, 48). One transporter involved in intestinal Pi absorption is the type IIb sodium-coupled Pi cotransporter (NaPi-IIb), which has been cloned from rodents and humans (20, 25, 28, 55). Pi absorption is modulated by many physiological factors, including hormonal and dietary factors (2). Glucocorticoids inhibit intestinal sodium-dependent Pi (Na/Pi) absorption (5, 38). EGF decreases intestinal Na/Pi absorption at least partially by inhibiting NaPi-IIb mRNA expression (56). Estrogen also plays a possible role in regulating intestinal Pi absorption (41). Phosphate content of the diet also regulates intestinal Pi absorption, and Pi deprivation stimulates intestinal Na/Pi absorption (10, 37, 42, 44, 49).
Vitamin D3, a steroid hormone, plays a central role in modulating phosphate homeostasis and Pi uptake by the small intestine (1, 19). The active form of vitamin D3 is 1,25-(OH)2 vitamin D3, which is mainly synthesized in kidney from 25-(OH) vitamin D3. 1,25-(OH)2 vitamin D3 binds the vitamin D receptor (VDR) to elicit its effect on regulation of gene expression. 1,25-(OH)2 vitamin D3 plays important roles in calcium and phosphate homeostasis, regulation of the parathyroid hormone system, inhibition of cell growth, and induction of cellular differentiation (9). Many previous studies showed that 1,25-(OH)2 vitamin D3 increases intestinal Pi absorption through modulation of Na/Pi absorption (13, 16, 17, 22, 23, 27, 30, 33, 34, 39, 40, 52). In adult rodents, this increase is at least partially mediated by modulation of NaPi-IIb protein expression (26). However, there is a lack of evidence demonstrating direct regulation of NaPi-IIb gene expression by 1,25-(OH)2 vitamin D3.
As reported in the current communication, we initially detected ontogenic changes in NaPi-IIb gene expression in rats and a significant increase in NaPi-IIb mRNA abundance and brush-border membrane Na/Pi uptake in 1,25-(OH)2 vitamin D3-treated suckling rats. These results suggested a possible role for 1,25-(OH)2 vitamin D3 in transcriptional regulation of the NaPi-IIb gene in young animals. To further understand the role of 1,25-(OH)2 vitamin D3 in intestinal Pi absorption, we characterized NaPi-IIb expression in rat intestinal epithelial (RIE) cells and developed this cell line as an in vitro model to determine the molecular mechanism of gene regulation by 1,25-(OH)2 vitamin D3. These are the first studies that exemplify age-dependent transcriptional regulation of NaPi-IIb gene expression by 1,25-(OH)2 vitamin D3.
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MATERIALS AND METHODS |
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Animals. Sprague-Dawley rats at 2, 3, and 6 wk and 95-100 days of age were used for these studies. Two-week-old and adult (90-100 days) rats were used for 1,25-(OH)2 vitamin D3 studies. Animals received subcutaneous injections of 1,25-(OH)2 vitamin D3 (6 µg/kg body wt, 1 dose; Sigma, St. Louis, MO) or vehicle [ethanol-propylene glycol (1:4, vol/vol)]. Sixteen hours after the injection, rats were killed and jejunal mucosa was harvested and used for mRNA and brush-border membrane vesicle (BBMV) purification. All animal work was approved by the University of Arizona Institutional Animal Care and Use Committee.
Cell culture. RIE cells were a gift from Dr. Raymond DuBois (Dept. of Medicine; Vanderbilt University, Nashville, TN). RIE cells are nontransformed, epithelium-derived cells isolated from the small intestinal epithelium of a 20-day-old rat (3). They were cultured as previously described (57). Media and other reagents used for cell culture were purchased from Irvine Scientific (Irvine, CA). In 1,25-(OH)2 vitamin D3 treatment experiments, cells were incubated with 100 nM 1,25-(OH)2 vitamin D3 for 16 h before cells were harvested. For transcriptional assays, cells were pretreated with actinomycin D (100 nM; Calbiochem-Novabiochem; San Diego, CA) for 2 h and then treated with 100 nM 1,25-(OH)2 vitamin D3 for 16 h in the presence of actinomycin D before cells were harvested.
RNA purification and Northern blot analyses. mRNA was isolated from RIE cells and rat jejunal mucosa with the Fast-Track mRNA purification kit (Invitrogen; Carlsbad, CA). Ten micrograms of mRNA was used for Northern blot analyses with rat NaPi-IIb cDNA probes (56) under high-stringency washing conditions (several washes with a 0.1× sodium chloride-sodium citrate-0.1% SDS solution at 65°C) as described previously (11). 1B15 (encoding rat cyclophilin; Ref. 15) cDNA-specific probes were used as internal standards for quantitating NaPi-IIb gene expression. Blots were exposed to a phosphorimaging screen, and band intensities were determined with Quantity One software (FX Molecular Imager; Bio-Rad, Hercules, CA). NaPi-IIb gene expression levels were estimated by taking the ratio of hybridization intensities of NaPi-IIb mRNA over 1B15 mRNA. The experiment was repeated three times with mRNA isolation from different groups of animals.
Na/Pi uptake analysis in BBMVs. BBMVs were prepared from rat jejunal mucosa, and Na/Pi uptake was carried out as previously described (4, 24, 36). The contribution of Na/Pi uptake was calculated by subtracting the sodium-independent uptake values observed in the absence of sodium from the uptake values in the presence of sodium. The experiment was repeated three times with BBMV isolated from different groups of animals.
PCR analysis to detect NaPi-IIb expression in RIE
cells.
mRNA was purified from RIE cells cultured in normal medium. RT-PCR
conditions were identical to those described in a previous publication
(56). The primers used to detect NaPi-IIb were
designed from rat NaPi-IIb cDNA (GenBank accession no.
AF157026). The forward primer was at 1446-1465 bp
(5'-AGCCCAGGCAACACATTGA-3'), and the reverse primer was at
1899-1917 bp (5'-ACACCATGCAGCAGACACG-3'). The expected
amplification size from NaPi-IIb mRNA is 472 bp. The
primers used to detect -actin were purchased from Stratagene (La
Jolla, CA). The size of the amplified product from the
-actin gene
is 661 bp.
Semiquantitative RT-PCR analysis of NaPi-IIb gene
expression.
mRNA was purified from RIE cells treated for 16 h with vehicle
(ethanol) or 1,25-(OH)2 vitamin D3 (100 nM).
RT-PCR conditions were described previously (56).
Subsaturation levels of cDNA templates needed to produce a
dose-dependent amount of PCR product were defined in initial
experiments by testing a range of template concentrations. Subsequent
PCR was carried out with subsaturation levels of RT reactions with
identical amplification parameters. PCR was performed with rat
NaPi-IIb or -actin primers in separate reactions; equal
volumes of both PCR reactions were loaded on the same gel and
visualized with ethidium bromide, and the optical density of each band
was determined by gel-doc analysis. NaPi-IIb mRNA
expression levels were estimated by taking a ratio of
NaPi-IIb over
-actin amplicon optical densities.
Construction of reporter plasmids.
Reporter plasmids used in this study were derived from pGL3-Basic
(Promega), which contains the firefly luciferase reporter gene. The
human NaPi-IIb promoter-reporter constructs pGL3/2783 bp,
pGL3/
1103 bp, and pGL3/
181 bp were made by restriction enzyme digestion and PCR (56). The 3'-end of all constructs ends
at +15 bp of the human NaPi-IIb gene. All constructs were
confirmed by sequencing on both strands.
Transient transfection and functional promoter analysis. RIE cells were cultured in 24-well plates. When cells reached 70-80% confluence, liposome-mediated transfection was performed as follows. Promoter vector DNA (0.5 µg), pRL-CMV (30 ng, Renilla luciferase reporter construct used as an internal standard; Promega), and Lipofectamine (5 µl; GIBCO BRL, Grand Island, NY) were mixed with 200 µl of Opti-MEM medium (GIBCO BRL) for 30 min at room temperature. The mixture was then added to the cells, and they were incubated for 5 h, followed by the addition of an equal volume of Dulbecco's modified Eagle's medium (DMEM) containing 20% fetal bovine serum (FBS). The next day, the medium was removed and replaced with standard medium with 10% FBS. Twenty-four hours later, cells were harvested for reporter gene assays. For 1,25-(OH)2 vitamin D3 treatment, 100 nM 1,25-(OH)2 vitamin D3 or vehicle (ethanol) was added for 16 h before cells were harvested. Promoter reporter assays were performed using the Dual Luciferase assay kit according to the manufacturer's instructions (Promega). Luciferase activities were measured with a luminometer (Femtomaster FB 12; Berthold Detection System, Pforzheim, Germany), and all assays provided data that were well within the linear range of the instrument.
Statistical analysis. ANOVA post hoc tests (StatView 5.0.1 version; SAS Institute, Cary, NC) were used to compare values of the experimental data. P values of <0.05 were considered significant.
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RESULTS |
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Effect of age on NaPi-IIb gene expression in rat
jejunum.
Jejunal mRNAs from 2-wk, 3-wk, 6-wk, and adult rats were purified, and
Northern blot analyses were performed with NaPi-IIb- and
1B15-specific cDNA probes (Fig. 1).
Expression levels of NaPi-IIb mRNA were significantly
different among age groups, with highest expression seen in 2-wk-old
rats and expression levels gradually decreasing three- to fourfold into
adulthood.
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Effect of 1,25-(OH)2 vitamin D3 treatment
on BBMV phosphate absorption in rat jejunum.
Two-week-old and adult rats were treated with 1,25-(OH)2
vitamin D3, BBMVs were purified from jejunum, and
Na/Pi absorption was measured by a membrane filtration
method. Na/Pi uptake (in nmol Pi · mg
protein1 · 10 s
1) in suckling rats
was significantly higher than in adult rats (94.6 ± 4.7 in
2-wk-old rats vs. 30.4 ± 2.3 in adult rats; Fig. 2A). Vitamin D3
treatment increased Na/Pi absorption in both suckling and
adult rats (94.6 ± 4.7 for control vs. 232.5 ± 45.3 for
treated in 2-wk-old rats, 30.4 ± 2.3 for control vs. 67.2 ± 16.3 for treated in adult rats; Fig. 2A), with the fold
inductions being similar (Fig. 2B).
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Effect of 1,25-(OH)2 vitamin D3 treatment
on NaPi-IIb mRNA levels in rat jejunum.
Two-week-old and adult rats were treated with 1,25-(OH)2
vitamin D3, mRNA was purified from jejunal mucosa, and
Northern blots were performed with rat NaPi-IIb and 1B15
cDNA probes. Hybridization patterns clearly showed that intestinal
NaPi-IIb mRNA abundance significantly increased
approximately twofold in 1,25-(OH)2 vitamin D3-treated 2-wk-old-rats, but no change was detected in
adult rats (Fig. 3). Also, there was no
change in intestinal 1B15 mRNA abundance with vehicle or
1,25-(OH)2 vitamin D3 treatment.
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1,25-(OH)2 vitamin D3 treatment increases
NaPi-IIb mRNA abundance in RIE cells.
Preliminary results from RT-PCR indicated that RIE cells endogenously
express the NaPi-IIb gene (data not shown). Subsequently, NaPi-IIb mRNA expression in RIE cells after exposure to
vehicle or 1,25-(OH)2 vitamin D3 was assessed
by semiquantitative RT-PCR with rat NaPi-IIb and -actin
primers. Data showed that NaPi-IIb gene expression was
significantly increased in 1,25-(OH)2 vitamin D3-treated RIE cells compared with vehicle-treated cells,
and the increase was approximately twofold (Fig.
4).
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Actinomycin D treatment blocks NaPi-IIb mRNA increase
induced by 1,25-(OH)2 vitamin D3 treatment in
RIE cells.
To test whether the effect of 1,25-(OH)2 vitamin
D3 on NaPi-IIb gene expression is due to
transcriptional regulation, RIE cells were first treated with
actinomycin D and then treated with 1,25-(OH)2 vitamin
D3 in the presence of actinomycin D before cells were
harvested. NaPi-IIb abundances were determined by
semiquantitative RT-PCR with rat NaPi-IIb and -actin
primers. The results showed that the increase in NaPi-IIb
mRNA abundance induced by 1,25-(OH)2 vitamin D3
treatment was abolished by actinomycin D treatment (Fig.
5). In these experiments,
actinomycin D did not alter basal expression levels of either the
NaPi-IIb or
-actin genes in RIE cells.
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Human NaPi-IIb gene promoter analysis in RIE cells.
To determine whether the 5'-flanking region of the human
NaPi-IIb gene contains a functional promoter in RIE cells,
three constructs (pGL3/2783 bp, pGL3/
1103 bp, and pGL3/
181 bp)
were transfected by Lipofectamine into RIE cells (57).
Promoter reporter gene assays were performed 48 h after
transfection. The promoter assay data showed that all promoter
constructs were functional in RIE cells (Fig.
6A).
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DISCUSSION |
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Earlier studies indicated that intestinal Na/Pi absorption declined with age in several mammalian species (4, 6, 45). These observations suggested that the expression of the transport protein(s), which is responsible for Na/Pi absorption, likely decreases with age. Our data demonstrate that NaPi-IIb gene expression decreases with age, and this observation correlates well with the functional studies. Thus it seems likely that NaPi-IIb expression contributes to the ontogenic changes seen in intestinal Pi absorption.
Studies also showed that 1,25-(OH)2 vitamin D3 treatment stimulates intestinal Na/Pi absorption (13, 14, 16, 17, 22, 23, 27, 30, 33, 34, 39, 40, 52). More recently, two groups showed that the stimulation of intestinal Pi absorption by 1,25-(OH)2 vitamin D3 in adult rodents is not mediated by increases in NaPi-IIb gene expression (26, 32). Our results showed that 1,25-(OH)2 vitamin D3 treatment increased intestinal Na/Pi uptake in adult rats but not NaPi-IIb mRNA expression, which is comparable to these studies. The increase in Pi uptake is most likely the result of increased apical NaPi-IIb protein expression in adult animals (26). Our data also showed that 1,25-(OH)2 vitamin D3 treatment increased intestinal Na/Pi absorption and NaPi-IIb mRNA expression in suckling rats, which suggests that the effect of 1,25-(OH)2 vitamin D3 on NaPi-IIb gene expression is age specific.
To decipher the molecular mechanism of 1,25-(OH)2 vitamin D3 regulation of intestinal NaPi-IIb gene expression in suckling animals, we explored the RIE cell line as an in vitro model. Our results demonstrate that the NaPi-IIb gene is endogenously expressed in RIE cells and that it is 1,25-(OH)2 vitamin D3 responsive. Furthermore, we performed Na-Pi cotransport studies in RIE cells with 1,25-(OH)2 vitamin D3 treatment and found that activity was increased by ~25% and was blockable by actinomycin D treatment (data not shown). However, these data are difficult to interpret because RIE cells likely contain other endogenous Na-Pi cotransporters, including ubiquitously expressed type III Na-Pi cotransporters and possibly other unidentified Na-Pi cotransporters. It is further possible that this other Na-Pi cotransporter(s) may also be regulated by 1,25-(OH)2 vitamin D3 (as has been shown for the type III Na-Pi cotransporters; Ref. 32), and thus it is extremely difficult to assess the single contribution of NaPi-IIb cotransporters. Moreover, we could not selectively study the activity of NaPi-IIb in RIE cells, because no specific inhibitors are available at this time. Our intention was simply to demonstrate that RIE cells are a good in vitro model to study NaPi-IIb gene regulation by 1,25-(OH)2 vitamin D3, as exemplified by the facts that the cells endogenously express this gene and that the gene is 1,25-(OH)2 vitamin D3 responsive. However, these data suggest that other in vitro models would have to be developed to study posttranscriptional regulation of the NaPi-IIb gene.
In vivo studies in suckling rats and in vitro studies in RIE cells showed that 1,25-(OH)2 vitamin D3 treatment increases NaPi-IIb mRNA abundance by approximately twofold. Therefore, transcriptional regulation seems likely. Further studies showed that activation of NaPi-IIb gene expression by 1,25-(OH)2 vitamin D3 in RIE cells could be abolished by 100 nM actinomycin D, a transcriptional inhibitor. These results suggest that the increase in NaPi-IIb mRNA abundance induced by 1,25-(OH)2 vitamin D3 likely involves synthesis of new NaPi-IIb mRNA. Furthermore, transfection studies with human NaPi-IIb promoter constructs showed that 1,25-(OH)2 vitamin D3 increased NaPi-IIb gene promoter activity by ~1.6-fold in transiently transfected RIE cells. Together, these data indicate that the effect of 1,25-(OH)2 vitamin D3 on intestinal NaPi-IIb gene expression can be mediated by control of transcriptional initiation.
Transfection of cells with three NaPi-IIb gene promoter
constructs (pGL3/2783 bp, pGL3/
1103 bp, and pGL3/
181 bp) resulted in significant reporter gene expression. This finding suggests that the
basal promoter region of the NaPi-IIb gene is located within the
181 bp region in RIE cells, as was previously described in
Caco-2 cells (57). Interestingly, the promoter construct pGL3/
2783 bp showed lower activity in transfected RIE cells compared with Caco-2 cells (56). Furthermore, the two longer
promoter constructs (pGL3/
2783 bp and pGL3/
1103 bp) were responsive
to 1,25-(OH)2 vitamin D3 treatment, but the
smaller construct (pGL3/
181 bp) was unresponsive. This observation
suggests that the putative 1,25-(OH)2 vitamin
D3 response element(s) is located between 181 and 1103 bp
upstream of the transcriptional initiation site.
Vitamin D3 responsive elements (VDRE) have been identified
from many genes, including the human renal NaPi-IIa
(NaPi-3) gene (50), the rat osteocalcin (OSC) gene, the
mouse osteopontin (MOP) gene, the rat calbindin D-9k (CaBP) gene, and
the human parathyroid hormone (PTH) gene (18, 46). We
searched the human NaPi-IIb gene promoter region from 181
bp to
1103 bp for putative VDREs, but no classical VDR binding
sequences were identified. This may therefore classify the human
NaPi-IIb gene in a group of genes that are responsive to
1,25-(OH)2 vitamin D3 treatment but do not have
classic VDRE sequences in their promoter regions (8, 46,
51). These data may also suggest that there is a novel VDRE
present in this gene, or alternatively, the 1,25-(OH)2 vitamin D3 response could be mediated by a
trans-acting factor that acts independently of the VDR.
In summary, we showed that the decrease in Na/Pi absorption during development correlates with decreased NaPi-IIb gene expression in the intestinal mucosa. We also demonstrated that 1,25-(OH)2 vitamin D3 treatment increases NaPi-IIb mRNA abundance in suckling rats and RIE cells and NaPi-IIb gene promoter activity in transfected RIE cells. Because actinomycin D treatment blocked 1,25-(OH)2 vitamin D3-induced increases in NaPi-IIb mRNA expression in RIE cells, we hypothesize that a transcriptional mechanism is likely involved. Further studies will focus on identification of the responsive region in the promoter and the trans-acting factors involved in regulation of the NaPi-IIb gene by 1,25-(OH)2 vitamin D3.
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ACKNOWLEDGEMENTS |
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We sincerely thank Michael S. Inouye for help with BBMV preparation and BBMV phosphate uptake assays.
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FOOTNOTES |
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This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant R01-DK-33209-17 and the W. M. Keck Foundation.
Address for reprint requests and other correspondence: F. K. Ghishan, Dept. of Pediatrics, Steele Memorial Children's Research Center, Arizona Health Sciences Center, 1501 N. Campbell Ave., Tucson, AZ 85724 (E-mail: fghishan{at}peds.arizona.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
10.1152/ajpcell.00412.2001
Received 19 September 2001; accepted in final form 23 October 2001.
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REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Avila, EM,
Basantes SP,
and
Ferraris RP.
Cholecalciferol modulates plasma phosphate but not plasma vitamin D levels and intestinal phosphate absorption in rainbow trout (Oncorhynchus mykiss).
Gen Comp Endocrinol
114:
460-469,
1999[ISI][Medline].
2.
Barlet, JP,
Davicco MJ,
and
Coxam V.
Physiology of intestinal absorption of phosphorus in animals.
Reprod Nutr Dev
35:
475-489,
1995[ISI][Medline] [in French].
3.
Blay, J,
and
Brown KD.
Characterization of an epithelioid cell line derived from rat small intestine: demonstration of cytokeratin filaments.
Cell Biol Int
8:
551-560,
1984.
4.
Borowitz, SM,
and
Ghishan FK.
Maturation of jejunal phosphate transport by rat brush border membrane vesicles.
Pediatr Res
19:
1308-1312,
1985[Abstract].
5.
Borowitz, SM,
and
Granrud GS.
Glucocorticoids inhibit intestinal phosphate absorption in developing rabbits.
J Nutr
122:
1273-1279,
1992[ISI][Medline].
6.
Borowitz, SM,
and
Granrud GS.
Ontogeny of intestinal phosphate absorption in rabbits.
Am J Physiol Gastrointest Liver Physiol
262:
G847-G853,
1992
7.
Brandis, M,
Harmeyer J,
Kaune R,
Mohrmann M,
Murer H,
and
Zimolo Z.
Phosphate transport in brush-border membranes from control and rachitic pig kidney and small intestine.
J Physiol (Lond)
384:
479-490,
1987[Abstract].
8.
Brenza, HL,
Kimmel-Jehan C,
Jehan F,
Shinki T,
Wakino S,
Anazawa H,
Suda T,
and
DeLuca HF.
Parathyroid hormone activation of the 25-hydroxyvitamin D3-1-hydroxylase gene promoter.
Proc Natl Acad Sci USA
95:
1387-1391,
1998
9.
Brown, AJ,
Dusso A,
and
Slatopolsky E.
Vitamin D.
Am J Physiol Renal Physiol
277:
F157-F175,
1999
10.
Caverzasio, J,
Danisi G,
Straub RW,
Murer H,
and
Bonjour JP.
Adaptation of phosphate transport to low phosphate diet in renal and intestinal brush border membrane vesicles: influence of sodium and pH.
Pflügers Arch
409:
333-336,
1987[ISI][Medline].
11.
Collins, JF,
Honda T,
Knobel S,
Bulus NM,
Conary J,
DuBois R,
and
Ghishan FK.
Molecular cloning, sequencing, tissue distribution, and functional expression of a Na+/H+ exchanger (NHE-2).
Proc Natl Acad Sci USA
90:
3938-3942,
1993[Abstract].
12.
Cross, HS,
Debiec H,
and
Peterlik M.
Mechanism and regulation of intestinal phosphate absorption.
Miner Electrolyte Metab
16:
115-124,
1990[ISI][Medline].
13.
Cross, HS,
and
Peterlik M.
Differential response of enterocytes to vitamin D during embryonic development: induction of intestinal inorganic phosphate, D-glucose and calcium uptake.
Horm Metab Res
14:
649-652,
1982[ISI][Medline].
14.
Cross, HS,
and
Peterlik M.
Calcium and inorganic phosphate transport in embryonic chick intestine: triiodothyronine enhances the genomic action of 1,25-dihydroxycholecalciferol.
J Nutr
118:
1529-1534,
1988[ISI][Medline].
15.
Danielson, PE,
Forss-Petter S,
Brow MA,
Calavetta L,
Douglass J,
Milner RJ,
and
Sutcliffe JG.
p1B15: a cDNA clone of the rat mRNA encoding cyclophilin.
DNA (NY)
7:
261-267,
1988[ISI][Medline].
16.
Danisi, G,
Bonjour JP,
and
Straub RW.
Regulation of Na-dependent phosphate influx across the mucosal border of duodenum by 1,25-dihydroxycholecalciferol.
Pflügers Arch
388:
227-232,
1980[ISI][Medline].
17.
Danisi, G,
Caverzasio J,
Trechsel U,
Bonjour JP,
and
Straub RW.
Phosphate transport adaptation in rat jejunum and plasma level of 1,25-dihydroxyvitamin D3.
Scand J Gastroenterol
25:
210-215,
1990[ISI][Medline].
18.
Darwish, HM,
and
DeLuca HF.
Analysis of binding of the 1,25-dihydroxyvitamin D3 receptor to positive and negative vitamin D response elements.
Arch Biochem Biophys
334:
223-234,
1996[ISI][Medline].
19.
DeLuca, HF.
New developments in the vitamin D endocrine system.
J Am Diet Assoc
80:
231-237,
1982[ISI][Medline].
20.
Feild, JA,
Zhang L,
Brun KA,
Brooks DP,
and
Edwards RM.
Cloning and functional characterization of a sodium-dependent phosphate transporter expressed in human lung and small intestine.
Biochem Biophys Res Commun
258:
578-582,
1999[ISI][Medline].
21.
Fuchs, R,
and
Peterlik M.
Intestinal phosphate transport.
Adv Exp Med Biol
128:
381-390,
1980[Medline].
22.
Fuchs, R,
and
Peterlik M.
Vitamin D-induced phosphate transport in intestinal brush border membrane vesicles.
Biochem Biophys Res Commun
93:
87-92,
1980[ISI][Medline].
23.
Ghishan, FK.
Phosphate transport by plasma membranes of enterocytes during development: role of 1,25-dihydroxycholecalciferol.
Am J Clin Nutr
55:
873-877,
1992[Abstract].
24.
Guner, YS,
Kiela PR,
Xu H,
Collins JF,
and
Ghishan FK.
Differential regulation of renal sodium-phosphate transporter by glucocorticoids during rat ontogeny.
Am J Physiol Cell Physiol
277:
C884-C890,
1999
25.
Hashimoto, M,
Wang DY,
Kamo T,
Zhu Y,
Tsujiuchi T,
Konishi Y,
Tanaka M,
and
Sugimura H.
Isolation and localization of type IIb Na/Pi cotransporter in the developing rat lung.
Am J Pathol
157:
21-27,
2000
26.
Hattenhauer, O,
Traebert M,
Murer H,
and
Biber J.
Regulation of small intestinal Na-Pi type IIb cotransporter by dietary phosphate intake.
Am J Physiol Gastrointest Liver Physiol
277:
G756-G762,
1999
27.
Hildmann, B,
Storelli C,
Danisi G,
and
Murer H.
Regulation of Na+-Pi cotransport by 1,25-dihydroxyvitamin D3 in rabbit duodenal brush-border membrane.
Am J Physiol Gastrointest Liver Physiol
242:
G533-G539,
1982
28.
Hilfiker, H,
Hattenhauer O,
Traebert M,
Forster I,
Murer H,
and
Biber J.
Characterization of a murine type II sodium-phosphate cotransporter expressed in mammalian small intestine.
Proc Natl Acad Sci USA
95:
14564-14569,
1998
29.
Huber, K,
Walter C,
Schroder B,
Biber J,
Murer H,
and
Breves G.
Epithelial phosphate transporters in small ruminants.
Ann NY Acad Sci
915:
95-97,
2000
30.
Kabakoff, B,
Kendrick NC,
and
DeLuca HF.
1,25-Dihydroxyvitamin D3-stimulated active uptake of phosphate by rat jejunum.
Am J Physiol Endocrinol Metab
243:
E470-E475,
1982
31.
Karsenty, G,
Lacour B,
Ulmann A,
Pierandrei E,
and
Drueke T.
Direct in vitro effects of 1,25 (OH)2 vitamin D3 on phosphate transport in isolated enterocytes from normal or vitamin D deficient rats.
Adv Exp Med Biol
178:
181-188,
1984[ISI][Medline].
32.
Katai, K,
Miyamoto K,
Kishida S,
Segawa H,
Nii T,
Tanaka H,
Tani Y,
Arai H,
Tatsumi S,
Morita K,
Taketani Y,
and
Takeda E.
Regulation of intestinal Na+-dependent phosphate co-transporters by a low-phosphate diet and 1,25-dihydroxyvitamin D3.
Biochem J
343:
705-712,
1999[ISI][Medline].
33.
Lee, DB,
Walling MM,
Levine BS,
Gafter U,
Silis V,
Hodsman A,
and
Coburn JW.
Intestinal and metabolic effect of 1,25-dihydroxyvitamin D3 in normal adult rat.
Am J Physiol Gastrointest Liver Physiol
240:
G90-G96,
1981
34.
Matsumoto, T,
Fontaine O,
and
Rasmussen H.
Effect of 1,25-dihydroxyvitamin D3 on phosphate uptake into chick intestinal brush border membrane vesicles.
Biochim Biophys Acta
599:
13-23,
1980[ISI][Medline].
35.
Murer, H,
and
Biber J.
A molecular view of proximal tubular inorganic phosphate (Pi) reabsorption and of its regulation.
Pflügers Arch
433:
379-389,
1997[ISI][Medline].
36.
Nakagawa, N,
and
Ghishan FK.
Transport of phosphate by plasma membranes of the jejunum and kidney of the mouse model of hypophosphatemic vitamin D-resistant rickets.
Proc Soc Exp Biol Med
203:
328-335,
1993[Abstract].
37.
Nakagawa, N,
and
Ghishan FK.
Low phosphate diet upregulates the renal and intestinal sodium-dependent phosphate transporter in vitamin D-resistant hypophosphatemic mice.
Proc Soc Exp Biol Med
205:
162-167,
1994[Abstract].
38.
Nuti, R,
Vattimo A,
Turchetti V,
and
Righi G.
25-Hydroxycholecalciferol as an antagonist of adverse corticosteroid effects on phosphate and calcium metabolism in man.
J Endocrinol Invest
7:
445-448,
1984[ISI][Medline].
39.
Peterlik, M.
Phosphate transport by embryonic chick duodenum. Stimulation by vitamin D3.
Biochim Biophys Acta
514:
164-171,
1978[ISI][Medline].
40.
Peterlik, M,
and
Wasserman RH.
Effect of vitamin D3 and 1,25-dihydroxyvitamin D3 on intestinal transport of phosphate.
Adv Exp Med Biol
81:
323-332,
1977[Medline].
41.
Pike, JW,
Spanos E,
Colston KW,
MacIntyre I,
and
Haussler MR.
Influence of estrogen on renal vitamin D hydroxylases and serum 1,25-(OH)2 D3 in chicks.
Am J Physiol Endocrinol Metab Gastrointest Physiol
235:
E338-E343,
1978
42.
Quamme, GA.
Phosphate transport in intestinal brush-border membrane vesicles: effect of pH and dietary phosphate.
Am J Physiol Gastrointest Liver Physiol
249:
G168-G176,
1985[ISI][Medline].
43.
Schroder, B,
and
Breves G.
Mechanisms of phosphate uptake into brush-border membrane vesicles from goat jejunum.
J Comp Physiol [B]
166:
230-240,
1996[ISI][Medline].
44.
Schroder, B,
Breves G,
and
Rodehutscord M.
Mechanisms of intestinal phosphorus absorption and availability of dietary phosphorus in pigs.
Dtsch Tierarztl Wochenschr
103:
209-214,
1996[ISI][Medline].
45.
Schroder, B,
Hattenhauer O,
and
Breves G.
Phosphate transport in pig proximal small intestines during postnatal development: lack of modulation by calcitriol.
Endocrinology
139:
1500-1507,
1998
46.
Segaert, S,
and
Bouillon R.
Vitamin D and regulation of gene expression.
Curr Opin Clin Nutr Metab Care
1:
347-354,
1998[Medline].
47.
Shirazi-Beechey, SP,
Gorvel JP,
and
Beechey RB.
Intestinal phosphate transport: localization, properties and identification, a progress report.
Prog Clin Biol Res
252:
59-64,
1988[Medline].
48.
Shirazi-Beechey, SP,
Gorvel JP,
and
Beechey RB.
Phosphate transport in intestinal brush-border membrane.
J Bioenerg Biomembr
20:
273-288,
1988[ISI][Medline].
49.
Sriussadaporn, S,
Wong MS,
Pike JW,
and
Favus MJ.
Tissue specificity and mechanism of vitamin D receptor up-regulation during dietary phosphorus restriction in the rat.
J Bone Miner Res
10:
271-280,
1995[ISI][Medline].
50.
Taketani, Y,
Miyamoto K,
Tanaka K,
Katai K,
Chikamori M,
Tatsumi S,
Segawa H,
Yamamoto H,
Morita K,
and
Takeda E.
Gene structure and functional analysis of the human Na+/phosphate cotransporter.
Biochem J
324:
927-934,
1997[ISI][Medline].
51.
Takeyama, K,
Kitanaka S,
Sato T,
Kobori M,
Yanagisawa J,
and
Kato S.
25-Hydroxyvitamin D3 1-hydroxylase and vitamin D synthesis.
Science
277:
1827-1830,
1997
52.
Walling, MW,
and
Kimberg DV.
Effects of 1,25-dihydroxyvitamin D3 and Solanum glaucophyllum on intestinal calcium and phosphate transport and on plasma Ca, Mg and P levels in the rat.
Endocrinology
97:
1567-1576,
1975[Abstract].
53.
Werner, A,
Dehmelt L,
and
Nalbant P.
Na+-dependent phosphate cotransporters: the NaPi protein families.
J Exp Biol
201:
3135-3142,
1998
54.
Werner, A,
and
Kinne RK.
Evolution of the Na-Pi cotransport systems.
Am J Physiol Regulatory Integrative Comp Physiol
280:
R301-R312,
2001
55.
Xu, H,
Bai L,
Collins JF,
and
Ghishan FK.
Molecular cloning, functional characterization, tissue distribution, and chromosomal localization of a human, small intestinal sodium-phosphate (Na+-Pi) transporter (SLC34A2).
Genomics
62:
281-284,
1999[ISI][Medline].
56.
Xu, H,
Collins JF,
Bai L,
Kiela PR,
and
Ghishan FK.
Regulation of the human sodium-phosphate cotransporter NaPi-IIb gene promoter by epidermal growth factor.
Am J Physiol Cell Physiol
280:
C628-C636,
2001
57.
Xu, H,
Collins JF,
Bai L,
Kiela PR,
Lynch RM,
and
Ghishan FK.
Epidermal growth factor regulation of rat NHE2 gene expression.
Am J Physiol Cell Physiol
281:
C504-C513,
2001