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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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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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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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