Calcium Transporter 1 and Epithelial Calcium Channel Messenger Ribonucleic Acid Are Differentially Regulated by 1,25 Dihydroxyvitamin D3 in the Intestine and Kidney of Mice

Song, Yurong; Peng, Xiaorong; Porta, Angela; Takanaga, Hitomi; Peng, Ji‐Bin; Hediger, Matthias A.; Fleet, James C.; Christakos, Sylvia

doi:10.1210/en.2003-0314

Cited by 220 publications

(207 citation statements)

References 45 publications

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“…The relative mRNA level of TRPV5 and TRPV6 in tissues co-expressing these channels is different. For instance, in duodenum the TRPV5 mRNA levels are much lower than that of TRPV6 or even below detection levels (Song et al 2003;van Abel et al 2003;van Cromphaut et al 2001). In kidney, however, TRPV5 mRNA is at least 100 times higher expressed compared to TRPV6.…”

Section: Molecular Features Of Trpv5 and Trpv6mentioning

confidence: 97%

The epithelial calcium channels TRPV5 and TRPV6: regulation and implications for disease

Abel

Hoenderop

Bindels

2005

Naunyn-Schmiedeberg's Arch Pharmacol

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The epithelial Ca 2+ channels TRPV5 and TRPV6 represent a new family of Ca 2+ channels that belongs to the superfamily of transient receptor potential channels. TRPV5 and TRPV6 constitute the apical Ca 2+ entry mechanism in active Ca 2+ transport in kidney and intestine. The central role of TRPV5 and TRPV6 in active Ca 2+ (re)absorption makes it a prime target for regulation to maintain Ca 2+ balance. This review covers the hormonal regulation, interaction with accessory proteins and (patho)physiological implications of these epithelial Ca 2+ channels.

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Section: Molecular Features Of Trpv5 and Trpv6mentioning

confidence: 97%

The epithelial calcium channels TRPV5 and TRPV6: regulation and implications for disease

Abel

Hoenderop

Bindels

2005

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Previous studies on the effect of dietary calcium or vitamin D on expression of these calcium channels in the kidney have presented somewhat conflicting results. Some studies show that these genes are regulated by calcium but not 1,25-dihydroxyvitmain D 3 in mice lacking VDR (38), whereas others show that they are modulated by both calcium and 1,25-dihydroxyvitmain D 3 in WT mice (39) and in mice lacking 1␣-hydoxylase (5). A previous report also shows that levels of TRPV5 are not altered in CaBP-D28k(Ϫ/Ϫ) mice (32).…”

Section: Table II Physiological Parameters Of 2-month Old Wt Cabp-d2mentioning

confidence: 97%

Critical Role of Calbindin-D28k in Calcium Homeostasis Revealed by Mice Lacking Both Vitamin D Receptor and Calbindin-D28k

Zheng

Xie

et al. 2004

Journal of Biological Chemistry

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Calbindin (CaBP)-D28k and CaBP-D9k are cytosolic vitamin D-dependent calcium-binding proteins long thought to play an important role in transepithelial calcium transport. However, recent genetic studies suggest that CaBP-D28k is not essential for calcium metabolism. Genetic ablation of this gene in mice leads to no calcemic abnormalities. Genetic inactivation of the vitamin D receptor (VDR) gene leads to hypocalcemia, secondary hyperparathyroidism, rickets, and osteomalacia, accompanied by 90% reduction in renal CaBP-D9k expression but little change in CaBP-D28k. To address whether the role of CaBP-D28k in calcium homeostasis is compensated by CaBP-D9k, we generated VDR/CaBP-D28k double knockout (KO) mice, which expressed no CaBP-D28k and only 10% of CaBP-D9k in the kidney. On a regular diet, the double KO mice were more growth-retarded and 42% smaller in body weight than VDRKO mice and died prematurely at 2.5-3 months of age. Compared with VDRKO mice, the double KO mice had higher urinary calcium excretion and developed more severe secondary hyperparathyroidism and rachitic skeletal phenotype, which were manifested by larger parathyroid glands, higher serum parathyroid hormone levels, much lower bone mineral density, and more distorted growth plate with more osteoid formation in the trabecular region. On high calcium, high lactose diet, blood-ionized calcium levels were normalized in both VDRKO and the double KO mice; however, in contrast to VDRKO mice, the skeletal abnormalities were not completely corrected in the double KO mice. These results directly demonstrate that CaBP-D28k plays a critical role in maintaining calcium homeostasis and skeletal mineralization and suggest that its calcemic role can be mostly compensated by CaBP-D9k.It is well established that calcium homeostasis is primarily maintained by the vitamin D and parathyroid hormone (PTH) 1 endocrine systems. In this regard, the principal role of vitamin D is to regulate calcium transport in the intestine and kidney. Intestinal and renal distal tubular calcium transfer consists of a passive, concentration gradient-dependent paracellular transport and an active, ATP-dependent transcellular transport (1). The latter is largely regulated by vitamin D and is crucial when calcium supply is low. It is believed that the vitamin D-mediated transcellular calcium transport in the duodenum and renal distal tubules involves three sequential steps: entry, intracellular movement, and extrusion. Influx of luminal calcium into the epithelial cells is propelled by a steep electrochemical gradient across the apical membrane, saturable at high levels of luminal calcium, and mediated by apical calcium channels (2-4). Once in the cytosol, calcium binds to the vitamin D-dependent calcium-binding proteins, calbindins (CaBPs), which ferry calcium from the apical to the basolateral portion of the cell, where the Na ϩ /Ca 2ϩ exchanger and Ca 2ϩ -dependent ATPase on the basolateral membrane extrude calcium into extracellular fluids (5-7). It is believed that the apical to b...

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“…These components have been put together in a diagrammatic fashion to present the current hypothesis of how 1,25-(OH) 2 D 3 stimulates active intestinal calcium absorption. TRPV6 is a calcium channel protein clearly induced by 1,25-(OH) 2 D 3 (12). Calcium entering through this channel is believed to associate with calbindin D 9k , which serves as a shuttle for calcium, presenting it to the basal lateral membrane calcium ATPase.…”

Section: Microarrays ͉ Trpv6 Ko Mice ͉ Vitamin D ͉ Vitamin D Mechanismentioning

confidence: 99%

TRPV6 is not required for 1α,25-dihydroxyvitamin D ₃ -induced intestinal calcium absorption in vivo

Kutuzova

Sundersingh

Vaughan

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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The requirement for TRPV6 for vitamin D-dependent intestinal calcium absorption in vivo has been examined by using vitamin D-deficient TRPV6 null mice and littermate wild-type mice. Each of the vitamin D-deficient animals received each day for 4 days 50 ng of 1,25-dihydroyvitamin D 3 in 0.1 ml of 95% propylene glycol:5% ethanol vehicle or vehicle only. Both the wild-type and TRPV6 null mice responded equally well to 1,25-dihydroxyvitamin D 3 in increasing intestinal calcium absorption. These results, along with our microarray data, demonstrate that TRPV6 is not required for vitamin D-induced intestinal calcium absorption and may not carry out a significant role in this process. These and previous results using calbindin D9k null mutant mice illustrate that molecular events in the intestinal calcium absorption process in response to the active form of vitamin D remain to be defined.A primary function of vitamin D is to markedly increase intestinal absorption of calcium and phosphate (1). During the 1950s, this absorption was shown to be primarily an active calcium transport process and an independent active phosphate transport process (2, 3). With the discovery of the vitamin D endocrine system came the understanding that this process was directly stimulated by the hormonal form of vitamin D, 1␣,25-dihydroxyvitamin D 3 (1,25-(OH) 2 D 3 ) (4). Because this hormonal form of vitamin D is regulated in response to the need for calcium, it became clear that the endogenous factor discovered by Nicolaysen and Egg-Larsen is the vitamin D endocrine system producing the final vitamin D hormone, 1,25-(OH) 2 D 3 (4, 5). There is still debate whether vitamin D further influences the diffusional component of calcium absorption, taking place at high intestinal levels of calcium (6, 7).The molecular mechanism underlying active calcium transport in response to vitamin D began unraveling with the discovery of calbindin D 9k by Wasserman and colleagues (8). Schachter and colleagues (9) also found a transporter responsive to vitamin D. Others have reported that vitamin D stimulates the basal lateral membrane calcium ATPase believed to be a calcium transporter (10, 11). These components have been put together in a diagrammatic fashion to present the current hypothesis of how 1,25-(OH) 2 D 3 stimulates active intestinal calcium absorption. TRPV6 is a calcium channel protein clearly induced by 1,25-(OH) 2 D 3 (12). Calcium entering through this channel is believed to associate with calbindin D 9k , which serves as a shuttle for calcium, presenting it to the basal lateral membrane calcium ATPase. This step provides the energy input for the transfer of calcium against a concentration gradient. All three of these genes are clearly under the influence of the active form of vitamin D (13). Unfortunately not all evidence is currently in support of this hypothesis. Transgenic mice in which calbindin D 9k has been eliminated have shown that calbindin D 9k is not required for 1,25-(OH) 2 D 3 -stimulated intestinal calcium absorption (14, 15). Fo...

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Calcium Transporter 1 and Epithelial Calcium Channel Messenger Ribonucleic Acid Are Differentially Regulated by 1,25 Dihydroxyvitamin D3 in the Intestine and Kidney of Mice

Cited by 220 publications

References 45 publications

The epithelial calcium channels TRPV5 and TRPV6: regulation and implications for disease

The epithelial calcium channels TRPV5 and TRPV6: regulation and implications for disease

Critical Role of Calbindin-D28k in Calcium Homeostasis Revealed by Mice Lacking Both Vitamin D Receptor and Calbindin-D28k

TRPV6 is not required for 1α,25-dihydroxyvitamin D ₃ -induced intestinal calcium absorption in vivo

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Calcium Transporter 1 and Epithelial Calcium Channel Messenger Ribonucleic Acid Are Differentially Regulated by 1,25 Dihydroxyvitamin D3 in the Intestine and Kidney of Mice

Cited by 220 publications

References 45 publications

The epithelial calcium channels TRPV5 and TRPV6: regulation and implications for disease

The epithelial calcium channels TRPV5 and TRPV6: regulation and implications for disease

Critical Role of Calbindin-D28k in Calcium Homeostasis Revealed by Mice Lacking Both Vitamin D Receptor and Calbindin-D28k

TRPV6 is not required for 1α,25-dihydroxyvitamin D 3 -induced intestinal calcium absorption in vivo

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TRPV6 is not required for 1α,25-dihydroxyvitamin D ₃ -induced intestinal calcium absorption in vivo