Transcriptome-Wide Profile of 25-Hydroxyvitamin D3 in Primary Immune Cells from Human Peripheral Blood

Vitamin D3 is an essential micronutrient mediating pleiotropic effects in multiple tissues and cell types via its metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), which activates the transcription factor v...

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Autores principales:	Andrea Hanel, Igor Bendik, Carsten Carlberg
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Vitamin D<sub>3</sub> 25-hydroxyvitamin D<sub>3</sub> 1α,25-dihydroxyvitamin D<sub>3</sub> transcriptome PBMCs vitamin D target genes Nutrition. Foods and food supply TX341-641
Acceso en línea:	https://doaj.org/article/c7302acb0a45425e94adb86602ce9b87
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spelling	oai:doaj.org-article:c7302acb0a45425e94adb86602ce9b872021-11-25T18:36:45ZTranscriptome-Wide Profile of 25-Hydroxyvitamin D<sub>3</sub> in Primary Immune Cells from Human Peripheral Blood10.3390/nu131141002072-6643https://doaj.org/article/c7302acb0a45425e94adb86602ce9b872021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6643/13/11/4100https://doaj.org/toc/2072-6643Vitamin 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>.Andrea HanelIgor BendikCarsten CarlbergMDPI AGarticleVitamin D<sub>3</sub>25-hydroxyvitamin D<sub>3</sub>1α,25-dihydroxyvitamin D<sub>3</sub>transcriptomePBMCsvitamin D target genesNutrition. Foods and food supplyTX341-641ENNutrients, Vol 13, Iss 4100, p 4100 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Vitamin D<sub>3</sub> 25-hydroxyvitamin D<sub>3</sub> 1α,25-dihydroxyvitamin D<sub>3</sub> transcriptome PBMCs vitamin D target genes Nutrition. Foods and food supply TX341-641
spellingShingle	Vitamin D<sub>3</sub> 25-hydroxyvitamin D<sub>3</sub> 1α,25-dihydroxyvitamin D<sub>3</sub> transcriptome PBMCs vitamin D target genes Nutrition. Foods and food supply TX341-641 Andrea Hanel Igor Bendik Carsten Carlberg Transcriptome-Wide Profile of 25-Hydroxyvitamin D<sub>3</sub> in Primary Immune Cells from Human Peripheral Blood
description	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>.
format	article
author	Andrea Hanel Igor Bendik Carsten Carlberg
author_facet	Andrea Hanel Igor Bendik Carsten Carlberg
author_sort	Andrea Hanel
title	Transcriptome-Wide Profile of 25-Hydroxyvitamin D<sub>3</sub> in Primary Immune Cells from Human Peripheral Blood
title_short	Transcriptome-Wide Profile of 25-Hydroxyvitamin D<sub>3</sub> in Primary Immune Cells from Human Peripheral Blood
title_full	Transcriptome-Wide Profile of 25-Hydroxyvitamin D<sub>3</sub> in Primary Immune Cells from Human Peripheral Blood
title_fullStr	Transcriptome-Wide Profile of 25-Hydroxyvitamin D<sub>3</sub> in Primary Immune Cells from Human Peripheral Blood
title_full_unstemmed	Transcriptome-Wide Profile of 25-Hydroxyvitamin D<sub>3</sub> in Primary Immune Cells from Human Peripheral Blood
title_sort	transcriptome-wide profile of 25-hydroxyvitamin d<sub>3</sub> in primary immune cells from human peripheral blood
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c7302acb0a45425e94adb86602ce9b87
work_keys_str_mv	AT andreahanel transcriptomewideprofileof25hydroxyvitamindsub3subinprimaryimmunecellsfromhumanperipheralblood AT igorbendik transcriptomewideprofileof25hydroxyvitamindsub3subinprimaryimmunecellsfromhumanperipheralblood AT carstencarlberg transcriptomewideprofileof25hydroxyvitamindsub3subinprimaryimmunecellsfromhumanperipheralblood
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Transcriptome-Wide Profile of 25-Hydroxyvitamin D<sub>3</sub> in Primary Immune Cells from Human Peripheral Blood

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