The claudin‐16 channel gene is transcriptionally inhibited by 1,25‐dihydroxyvitamin D

Kladnitsky, Orly; Rozenfeld, Julia; Azulay-Debby, Hilla; Efrati, Edna; Zelikovic, Israel

doi:10.1113/expphysiol.2014.083394

Cited by 13 publications

(6 citation statements)

References 56 publications

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“…) and claudin‐16 (Kladnitsky et al. ); however, not all studies show this negative regulation (reviewed by Zhang et al. ), suggesting that the effects of 1,25(OH) 2 D might be context or site dependent and reflect the complex nature of the tight junction.…”

Section: Discussionmentioning

confidence: 99%

“…For example, claudin-2 protein was inhibited by in vitro treatment of duodenal cells with 1,25(OH) 2 D (Du et al 2015). Other claudins can be negatively regulated by 1,25(OH) 2 D, including claudin-5 (Won et al 2015) and claudin-16 (Kladnitsky et al 2015); however, not all studies show this negative regulation (reviewed by Zhang et al 2013), suggesting that the effects of 1,25(OH) 2 D might be context or site dependent and reflect the complex nature of the tight junction. Future studies may also choose to validate the reduced claudin-1 protein levels we observed (using immunofluorescence) by other means (e.g., western blot), and measure the effects of vitamin D supplementation on the expression of other claudins and proteins associated with the tight junction.…”

Section: Discussionmentioning

confidence: 99%

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Vitamin D supplementation of initially vitamin D-deficient mice diminishes lung inflammation with limited effects on pulmonary epithelial integrity

et al. 2017

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In disease settings, vitamin D may be important for maintaining optimal lung epithelial integrity and suppressing inflammation, but less is known of its effects prior to disease onset. Female BALB/c dams were fed a vitamin D3‐supplemented (2280 IU/kg, VitD+) or nonsupplemented (0 IU/kg, VitD−) diet from 3 weeks of age, and mated at 8 weeks of age. Male offspring were fed the same diet as their mother. Some offspring initially fed the VitD− diet were switched to a VitD+ diet from 8 weeks of age (VitD−/+). At 12 weeks of age, signs of low‐level inflammation were observed in the bronchoalveolar lavage fluid (BALF) of VitD− mice (more macrophages and neutrophils), which were suppressed by subsequent supplementation with vitamin D3. There was no difference in the level of expression of the tight junction proteins occludin or claudin‐1 in lung epithelial cells of VitD+ mice compared to VitD− mice; however, claudin‐1 levels were reduced when initially vitamin D‐deficient mice were fed the vitamin D3‐containing diet (VitD−/+). Reduced total IgM levels were detected in BALF and serum of VitD−/+ mice compared to VitD+ mice. Lung mRNA levels of the vitamin D receptor (VDR) were greatest in VitD−/+ mice. Total IgG levels in BALF were greater in mice fed the vitamin D3‐containing diet, which may be explained by increased activation of B cells in airway‐draining lymph nodes. These findings suggest that supplementation of initially vitamin D‐deficient mice with vitamin D3 suppresses signs of lung inflammation but has limited effects on the epithelial integrity of the lungs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Vitamin D supplementation of initially vitamin D-deficient mice diminishes lung inflammation with limited effects on pulmonary epithelial integrity

et al. 2017

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“…2013) and Mg 2+ (claudin‐16: Kladnitsky et al . 2015). Recently, the increase in intestinal absorption of P i (and Ca 2+ ) induced by lithocholic acid was reported to require the Vdr but to be independent of NaPi‐IIb (Hashimoto et al .…”

Section: Introductionmentioning

confidence: 99%

1,25(OH)₂ vitamin D₃ stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine

Hernando

Pastor-Arroyo

Marks

et al. 2020

The Journal of Physiology

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Key points Intestinal absorption of phosphate proceeds via an active/transcellular route mostly mediated by NaPi‐IIb/Slc34a2 and a poorly characterized passive/paracellular pathway. Intestinal phosphate absorption and expression of NaPi‐IIb are stimulated by 1,25(OH)2 vitamin D3 but whether NaPi‐IIb is the only target under hormonal control remains unknown. We report that administration of 1,25(OH)2 vitamin D3 to wild‐type mice resulted in the expected increase in active transport of phosphate in jejunum, without changing paracellular fluxes. Instead, the same treatment failed to alter phosphate transport in intestinal‐depleted Slc34a2‐deficient mice. In both genotypes, 1,25(OH)2 vitamin D3 induced similar hyperphosphaturic responses and changes in the plasma levels of FGF23 and PTH. While urinary phosphate loss induced by administration of 1,25(OH)2 vitamin D3 did not alter plasma phosphate, further studies should investigate whether chronic administration would lead to phosphate imbalance in mice with reduced active intestinal absorption. Abstract Intestinal absorption of phosphate is stimulated by 1,25(OH)2 vitamin D3. At least two distinct mechanisms underlie phosphate absorption in the gut, an active transcellular transport requiring the Na+/phosphate cotransporter NaPi‐IIb/Slc34a2, and a poorly characterized paracellular passive pathway. 1,25(OH)2 vitamin D3 stimulates NaPi‐IIb expression and function, and loss of NaPi‐IIb reduces intestinal phosphate absorption. However, it is remains unknown whether NaPi‐IIb is the only target for hormonal regulation by 1,25(OH)2 vitamin D3. Here we compared the effects of intraperitoneal administration of 1,25(OH)2 vitamin D3 (2 days, once per day) in wild‐type and intestinal‐specific Slc34a2‐deficient mice, and analysed trans‐ vs. paracellular routes of phosphate absorption. We found that treatment stimulated active transport of phosphate only in jejunum of wild‐type mice, though NaPi‐IIb protein expression was upregulated in jejunum and ileum. In contrast, 1,25(OH)2 vitamin D3 administration had no effect in Slc34a2‐deficient mice, suggesting that the hormone specifically regulates NaPi‐IIb expression. In both groups, 1,25(OH)2 vitamin D3 elicited the expected increase of plasma fibroblast growth factor 23 (FGF23) and reduction of parathyroid hormone (PTH). Treatment resulted in hyperphosphaturia (and hypercalciuria) in both genotypes, though mice remained normophosphataemic. While increased intestinal absorption and higher FGF23 can trigger the hyperphosphaturic response in wild types, only higher FGF23 can explain the renal response in Slc34a2‐deficient mice. Thus, 1,25(OH)2 vitamin D3 stimulates intestinal phosphate absorption by acting on the active transcellular pathway mostly mediated by NaPi‐IIb while the paracellular pathway appears not to be affected.

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“…Hypomagnesaemia in mice increases both claudin-16 protein and mRNA abundance, while Mg 2+ -loaded animals down-regulated claudin-16 ( 153 ) . The expression of claudin-16 is inhibited by calcitriol ( 154 ) and further influenced by a variety of hormones such as glucagon, insulin, calcitonin, vasopressin or isoproterenol ( 155 ) , which makes it difficult to evaluate these effects in vivo . Furthermore, Ca 2+ transport via claudin-16 is reduced by Mg 2+ ( 156 ) : ‘A competitive transport of Mg 2+ and Ca 2+ via the common paracellular route in TAL could explain the coupling between Mg 2+ and Ca 2+ excretion’ ( 157 ) (see below).…”

Section: Urinary Mg2+ Excretionmentioning

confidence: 99%

Magnesium homeostasis in cattle: absorption and excretion

et al. 2018

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Magnesium (Mg2+) is an essential mineral without known specific regulatory mechanisms. In ruminants, plasma Mg2+ concentration depends primarily on the balance between Mg2+ absorption and Mg2+ excretion. The primary site of Mg2+ absorption is the rumen, where Mg2+ is apically absorbed by both potential-dependent and potential-independent uptake mechanisms, reflecting involvement of ion channels and electroneutral transporters, respectively. Transport is energised in a secondary active manner by a basolateral Na+/Mg2+ exchanger. Ruminal transport of Mg2+ is significantly influenced by a variety of factors such as high K+ concentration, sudden increases of ammonia, pH, and the concentration of SCFA. Impaired Mg2+ absorption in the rumen is not compensated for by increased transport in the small or large intestine. While renal excretion can be adjusted to compensate precisely for any surplus in Mg2+ uptake, a shortage in dietary Mg2+ cannot be compensated for either via skeletal mobilisation of Mg2+ or via up-regulation of ruminal absorption. In such situations, hypomagnesaemia will lead to decrease of a Mg2+ in the cerebrospinal fluid and clinical manifestations of tetany. Improved knowledge concerning the factors governing Mg2+ homeostasis will allow reliable recommendations for an adequate Mg2+ intake and for the avoidance of possible disturbances. Future research should clarify the molecular identity of the suggested Mg2+ transport proteins and the regulatory mechanisms controlling renal Mg excretion as parameters influencing Mg2+ homeostasis.

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The claudin‐16 channel gene is transcriptionally inhibited by 1,25‐dihydroxyvitamin D

Abstract: New Findings r What is the central question of this study?In the kidney, the bulk of the filtered Mg 2+ is reabsorbed in the thick ascending limb by paracellular conductance, mediated by the tight junction protein, claudin-16, which is encoded by the gene CLDN16.

Cited by 13 publications

References 56 publications

Vitamin D supplementation of initially vitamin D-deficient mice diminishes lung inflammation with limited effects on pulmonary epithelial integrity

Vitamin D supplementation of initially vitamin D-deficient mice diminishes lung inflammation with limited effects on pulmonary epithelial integrity

1,25(OH)₂ vitamin D₃ stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine

Magnesium homeostasis in cattle: absorption and excretion

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The claudin‐16 channel gene is transcriptionally inhibited by 1,25‐dihydroxyvitamin D

Abstract: New Findings r What is the central question of this study?In the kidney, the bulk of the filtered Mg 2+ is reabsorbed in the thick ascending limb by paracellular conductance, mediated by the tight junction protein, claudin-16, which is encoded by the gene CLDN16.

Cited by 13 publications

References 56 publications

Vitamin D supplementation of initially vitamin D-deficient mice diminishes lung inflammation with limited effects on pulmonary epithelial integrity

Vitamin D supplementation of initially vitamin D-deficient mice diminishes lung inflammation with limited effects on pulmonary epithelial integrity

1,25(OH)2 vitamin D3 stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine

Magnesium homeostasis in cattle: absorption and excretion

Contact Info

Product

Resources

About

1,25(OH)₂ vitamin D₃ stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine