Transcriptome-Wide Profile of 25-Hydroxyvitamin D<sub>3</sub> in Primary Immune Cells from Human Peripheral Blood
Vitamin D<sub>3</sub> is an essential micronutrient mediating pleiotropic effects in multiple tissues and cell types via its metabolite 1α,25-dihydroxyvitamin D<sub>3</sub> (1,25(OH)<sub>2</sub>D<sub>3</sub>), which activates the transcription factor v...
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| Autores principales: | , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/c7302acb0a45425e94adb86602ce9b87 |
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| Sumario: | Vitamin D<sub>3</sub> is an essential micronutrient mediating pleiotropic effects in multiple tissues and cell types via its metabolite 1α,25-dihydroxyvitamin D<sub>3</sub> (1,25(OH)<sub>2</sub>D<sub>3</sub>), which activates the transcription factor vitamin D receptor. In this study, we used peripheral blood mononuclear cells (PBMCs) obtained from five healthy adults and investigated transcriptome-wide, whether the precursor of 1,25(OH)<sub>2</sub>D<sub>3</sub>, 25-hydroxyvitamin D<sub>3</sub> (25(OH)D<sub>3</sub>), has gene regulatory potential on its own. Applying thresholds of >2 in fold change of gene expression and <0.05 as a false discovery rate, in this ex vivo approach the maximal physiological concentration of 25(OH)D<sub>3</sub> (250 nM (nmol/L)) none of the study participants had a significant effect on their PBMC transcriptome. In contrast, 1000 and 10,000 nM 25(OH)D<sub>3</sub> regulated 398 and 477 genes, respectively, which is comparable to the 625 genes responding to 10 nM 1,25(OH)<sub>2</sub>D<sub>3</sub>. The majority of these genes displayed specificity to the tested individuals, but not to the vitamin D metabolite. Interestingly, the genes <i>MYLIP</i> (myosin regulatory light chain interacting protein) and <i>ABCG1</i> (ATP binding cassette subfamily G member 1) showed to be specific targets of 10,000 nM 25(OH)D<sub>3</sub>. In conclusion, 100- and 1000-fold higher 25(OH)D<sub>3</sub> concentrations than the reference 10 nM 1,25(OH)<sub>2</sub>D<sub>3</sub> are able to affect the transcriptome of PBMCs with a profile comparable to that of 1,25(OH)<sub>2</sub>D<sub>3</sub>. |
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