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Serum sulfate level and Slc13a1 mRNA expression remain unaltered in a mouse model of moderate vitamin D deficiency

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Abstract

Sulfate is essential for healthy foetal growth and neurodevelopment. The SLC13A1 sulfate transporter is primarily expressed in the kidney where it mediates sulfate reabsorption and maintains circulating sulfate levels. To meet foetal demands, maternal sulfate levels increase by twofold in pregnancy via upregulated SLC13A1 expression. Previous studies found hyposulfataemia and reduced renal Slc13a1 mRNA expression in rodent models with either severe vitamin D deficiency or perturbed vitamin D signalling. Here we investigated a mouse model of moderate vitamin D deficiency. However, serum sulfate level and renal Slc13a1 mRNA expression was not decreased by a moderate reduction in circulating vitamin D level. We confirmed that the mouse Slc13a1 5’-flanking region was upregulated by 1,25(OH)2D3 using luciferase assays in a cultured renal OK cell line. These results support the presence of a functional VDRE in the mouse Slc13a1 but suggests that moderate vitamin D deficiency does not impact on sulfate homeostasis. As sulfate biology is highly conserved between rodents and humans, we proposed that human SLC13A1 would be under similar transcriptional regulation by 1,25(OH)2D3. Using an online prediction tool we identified a putative VDRE in the SLC13A1 5’-flanking region but unlike the mouse Slc13a1 sequence, the human sequence did not confer a significant response to 1,25(OH)2D3 in vitro. Overall, this study suggests that moderate vitamin D deficiency may not alter sulfate homeostasis. This needs to be confirmed in humans, particularly during pregnancy when vitamin D and sulfate levels need to be maintained at high levels for healthy maternal and child outcomes.

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References

  1. Langford R, Hurrion E, Dawson PA (2017) Genetics and pathophysiology of mammalian sulfate biology. J Genet Genom 44:7–20. https://doi.org/10.1016/j.jgg.2016.08.001

    Article  Google Scholar 

  2. Dawson PA, Elliott A, Bowling FG (2015) Sulphate in pregnancy. Nutrients 7:1594–1606. https://doi.org/10.3390/nu7031594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Dawson PA, Petersen S, Rodwell R, Johnson P, Gibbons K, McWhinney A, Bowling FG, McIntyre HD (2015) Reference intervals for plasma sulfate and urinary sulfate excretion in pregnancy. BMC Pregnancy Childbirth 15:96. https://doi.org/10.1186/s12884-015-0526-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Dawson PA, Sim P, Simmons DG, Markovich D (2011) Fetal loss and hyposulfataemia in pregnant NaS1 transporter null mice. J Reprod Dev 57:444–449. https://doi.org/10.1262/jrd.10-173k

    Article  CAS  PubMed  Google Scholar 

  5. Lee HJ, Balasubramanian SV, Morris ME (1999) Effect of pregnancy, postnatal growth, and gender on renal sulfate transport. Proc Soc Exp Biol Med 221:336–344. https://doi.org/10.1046/j.1525-1373.1999.d01-90.x

    Article  CAS  PubMed  Google Scholar 

  6. Murer H, Markovich D, Biber J (1994) Renal and small intestinal sodium-dependent symporters of phosphate and sulphate. J Exp Biol 196:167–181

    Article  CAS  PubMed  Google Scholar 

  7. Beck L, Silve C (2001) Molecular aspects of renal tubular handling and regulation of inorganic sulfate. Kidney Int 59:835–845. https://doi.org/10.1046/j.1523-1755.2001.059003835.x

    Article  CAS  PubMed  Google Scholar 

  8. Dawson PA, Rakoczy J, Simmons DG (2012) Placental, renal, and ileal sulfate transporter gene expression in mouse gestation. Biol Reprod 87:43. https://doi.org/10.1095/biolreprod.111.098749

    Article  CAS  PubMed  Google Scholar 

  9. Dawson PA, Markovich D (2002) Transcriptional regulation of the sodium-sulfate cotransporter NaS(i)-1 gene. Cell Biochem Biophys 36:175–182. https://doi.org/10.1385/cbb:36:2-3:175

    Article  CAS  PubMed  Google Scholar 

  10. Dawson PA, Markovich D (2002) Regulation of the mouse Nas1 promoter by vitamin D and thyroid hormone. Pflugers Arch 444:353–359. https://doi.org/10.1007/s00424-002-0789-x

    Article  CAS  PubMed  Google Scholar 

  11. Bolt MJ, Liu W, Qiao G, Kong J, Zheng W, Krausz T, Cs-Szabo G, Sitrin MD, Li YC (2004) Critical role of vitamin D in sulfate homeostasis: regulation of the sodium-sulfate cotransporter by 1,25-dihydroxyvitamin D3. Am J Physiol Endocrinol Metab 287:E744–E749. https://doi.org/10.1152/ajpendo.00151.2004

    Article  CAS  PubMed  Google Scholar 

  12. Fernandes I, Hampson G, Cahours X, Morin P, Coureau C, Couette S, Prie D, Biber J, Murer H, Friedlander G, Silve C (1997) Abnormal sulfate metabolism in vitamin D-deficient rats. J Clin Invest 100:2196–2203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Groves NJ, Kesby JP, Eyles DW, McGrath JJ, Mackay-Sim A, Burne TH (2013) Adult vitamin D deficiency leads to behavioural and brain neurochemical alterations in C57BL/6J and BALB/c mice. Behav Brain Res 241:120–131. https://doi.org/10.1016/j.bbr.2012.12.001

    Article  CAS  PubMed  Google Scholar 

  14. Groves NJ, Zhou M, Jhaveri DJ, McGrath JJ, Burne THJ (2017) Adult vitamin D deficiency exacerbates impairments caused by social stress in BALB/c and C57BL/6 mice. Psychoneuroendocrinology 86:53–63. https://doi.org/10.1016/j.psyneuen.2017.09.003

    Article  CAS  PubMed  Google Scholar 

  15. Dawson P, McWhinney A, Reimer M, Bowling F (2018) Evaluation of an ion chromatography method for quantitating sulfate in plasma. Serum Urine J Chromatogr. https://doi.org/10.4172/2157-7064.1000411

    Article  Google Scholar 

  16. Dawson PA, Rakoczy J, Simmons DG (2012) Placental, renal, and ileal sulfate transporter gene expression in mouse gestation. Biol Reprod 87:1–9

    Article  Google Scholar 

  17. Dawson PA, Weerasekera SJ, Atcheson RJ, Twomey SA, Simmons DG (2020) Molecular analysis of the human placental cysteine dioxygenase type 1 gene. Mol Genet and Metab Rep 22:100568. https://doi.org/10.1016/j.ymgmr.2020.100568

    Article  CAS  Google Scholar 

  18. Marshall PA, Hernandez Z, Kaneko I, Widener T, Tabacaru C, Aguayo I, Jurutka PW (2012) Discovery of novel vitamin D receptor interacting proteins that modulate 1,25-dihydroxyvitamin D3 signaling. J Steroid Biochem Mol Biol 132:147–159. https://doi.org/10.1016/j.jsbmb.2012.05.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Beck L, Markovich D (2000) The mouse Na(+)-sulfate cotransporter gene Nas1. Cloning, tissue distribution, gene structure, chromosomal assignment, and transcriptional regulation by vitamin D. J Biol Chem 275:11880–11890. https://doi.org/10.1074/jbc.275.16.11880

    Article  CAS  PubMed  Google Scholar 

  20. Haussler MR, Whitfield GK, Kaneko I, Haussler CA, Hsieh D, Hsieh JC, Jurutka PW (2013) Molecular mechanisms of vitamin D action. Calcif Tissue Int 92:77–98. https://doi.org/10.1007/s00223-012-9619-0

    Article  CAS  PubMed  Google Scholar 

  21. Chow EC, Quach HP, Vieth R, Pang KS (2013) Temporal changes in tissue 1α,25-dihydroxyvitamin D3, vitamin D receptor target genes, and calcium and PTH levels after 1,25(OH)2D3 treatment in mice. Am J Physiol Endocrinol Metab 304:E977–E989. https://doi.org/10.1152/ajpendo.00489.2012

    Article  CAS  PubMed  Google Scholar 

  22. Seldeen KL, Pang M, Rodríguez-Gonzalez M, Hernandez M, Sheridan Z, Yu P, Troen BR (2017) A mouse model of vitamin D insufficiency: is there a relationship between 25(OH) vitamin D levels and obesity? Nutr Metab (Lond) 14:26. https://doi.org/10.1186/s12986-017-0174-6

    Article  CAS  PubMed  Google Scholar 

  23. Peng L, Malloy PJ, Feldman D (2004) Identification of a functional vitamin D response element in the human insulin-like growth factor binding protein-3 promoter. Mol Endocrinol 18:1109–1119. https://doi.org/10.1210/me.2003-0344

    Article  CAS  PubMed  Google Scholar 

  24. Wang TT, Tavera-Mendoza LE, Laperriere D, Libby E, MacLeod NB, Nagai Y, Bourdeau V, Konstorum A, Lallemant B, Zhang R, Mader S, White JH (2005) Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol 19:2685–2695. https://doi.org/10.1210/me.2005-0106

    Article  CAS  PubMed  Google Scholar 

  25. Lee A, Dawson PA, Markovich D (2005) NaSi-1 and Sat-1: structure, function and transcriptional regulation of two genes encoding renal proximal tubular sulfate transporters. Int J Biochem Cell Biol 37:1350–1356. https://doi.org/10.1016/j.biocel.2005.02.013

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by Mater Research and the Mater Foundation, PAD is supported by a Mater Foundation Principal Research Fellowship. We acknowledge the administrative and IT support of Mater Research Ltd for this research that was carried out in part at the Translational Research Institute (TRI), which is supported by a grant from the Australian Government.

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Authors and Affiliations

  1. Mater Research Institute, The University of Queensland, Translational Research Institute, 37 Kent St, Woolloongabba, QLD, 4102, Australia

    Ranita J. Atcheson & Paul A. Dawson

  2. Queensland Brain Institute, The University of Queensland, St. Lucia, QLD, 4072, Australia

    Thomas H. J. Burne

  3. Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, QLD, 4076, Australia

    Thomas H. J. Burne

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  1. Ranita J. Atcheson
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  2. Thomas H. J. Burne
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  3. Paul A. Dawson
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by RJA and THJB. The first draft of the manuscript was written by RJA and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Paul A. Dawson.

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Atcheson, R.J., Burne, T.H.J. & Dawson, P.A. Serum sulfate level and Slc13a1 mRNA expression remain unaltered in a mouse model of moderate vitamin D deficiency. Mol Cell Biochem 478, 1771–1777 (2023). https://doi.org/10.1007/s11010-022-04634-7

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  • DOI: https://doi.org/10.1007/s11010-022-04634-7

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