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

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)(2)D-3 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)(2)D-3. 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)(2)D-3 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.

Automated summary

Sulfate is crucial for foetal growth and neurodevelopment, and the SLC13A1 sulfate transporter regulates sulfate reabsorption in the kidney. Previous studies showed that severe vitamin D deficiency affects sulfate homeostasis in rodents. However, this study found that moderate vitamin D deficiency did not impact sulfate levels or the expression of the SLC13A1 gene in mice. The researchers also discovered differences in the regulation of SLC13A1 between mouse and human cells, suggesting that the effects of vitamin D deficiency on sulfate homeostasis may vary between species.