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Relevance of Vitamin D Receptor Target Genes for Monitoring the Vitamin D Responsiveness of Primary Human Cells

Vitamin D(3) has transcriptome- and genome-wide effects and activates, via the binding of its metabolite 1α,25-dihydroxyvitamin D(3) to the transcription factor vitamin D receptor (VDR), several hundred target genes. Using samples from a 5-month vitamin D(3) intervention study (VitDmet), we recently...

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Autores principales: Vukić, Maja, Neme, Antonio, Seuter, Sabine, Saksa, Noora, de Mello, Vanessa D. F., Nurmi, Tarja, Uusitupa, Matti, Tuomainen, Tomi-Pekka, Virtanen, Jyrki K., Carlberg, Carsten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4395145/
https://www.ncbi.nlm.nih.gov/pubmed/25875760
http://dx.doi.org/10.1371/journal.pone.0124339
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author Vukić, Maja
Neme, Antonio
Seuter, Sabine
Saksa, Noora
de Mello, Vanessa D. F.
Nurmi, Tarja
Uusitupa, Matti
Tuomainen, Tomi-Pekka
Virtanen, Jyrki K.
Carlberg, Carsten
author_facet Vukić, Maja
Neme, Antonio
Seuter, Sabine
Saksa, Noora
de Mello, Vanessa D. F.
Nurmi, Tarja
Uusitupa, Matti
Tuomainen, Tomi-Pekka
Virtanen, Jyrki K.
Carlberg, Carsten
author_sort Vukić, Maja
collection PubMed
description Vitamin D(3) has transcriptome- and genome-wide effects and activates, via the binding of its metabolite 1α,25-dihydroxyvitamin D(3) to the transcription factor vitamin D receptor (VDR), several hundred target genes. Using samples from a 5-month vitamin D(3) intervention study (VitDmet), we recently reported that the expression of 12 VDR target genes in peripheral blood mononuclear cells (PBMCs) as well as 12 biochemical and clinical parameters of the study participants are significantly triggered by vitamin D(3). In this study, we performed a more focused selection of further 12 VDR target genes and demonstrated that changes of their mRNA expression in PBMCs of VitDmet subjects significantly correlate with alterations of 25-hydroxyvitamin D3 serum levels. Network and self-organizing map analysis of these datasets together with that of the other 24 parameters was followed by relevance calculations and identified changes in parathyroid hormone serum levels and the expression of the newly selected genes STS, BCL6, ITGAM, LRRC25, LPGAT1 and TREM1 as well as of the previously reported genes DUSP10 and CD14 as the most relevant parameters for describing vitamin D responsiveness in vivo. Moreover, parameter relevance ranking allowed the segregation of study subjects into high and low responders. Due to the long intervention period the vitamin D response was not too prominent on the level of transcriptional activation. Therefore, we performed in the separate VitDbol trial a short-term but high dose stimulation with a vitamin D3 bolus. In PBMCs of VitDbol subjects we observed direct transcriptional effects on the selected VDR target genes, such as an up to 2.1-fold increase already one day after supplementation onset. In conclusion, both long-term and short-term vitamin D(3) supplementation studies allow monitoring the vitamin D responsiveness of human individuals and represent new types of human in vivo vitamin D(3) investigations.
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spelling pubmed-43951452015-04-21 Relevance of Vitamin D Receptor Target Genes for Monitoring the Vitamin D Responsiveness of Primary Human Cells Vukić, Maja Neme, Antonio Seuter, Sabine Saksa, Noora de Mello, Vanessa D. F. Nurmi, Tarja Uusitupa, Matti Tuomainen, Tomi-Pekka Virtanen, Jyrki K. Carlberg, Carsten PLoS One Research Article Vitamin D(3) has transcriptome- and genome-wide effects and activates, via the binding of its metabolite 1α,25-dihydroxyvitamin D(3) to the transcription factor vitamin D receptor (VDR), several hundred target genes. Using samples from a 5-month vitamin D(3) intervention study (VitDmet), we recently reported that the expression of 12 VDR target genes in peripheral blood mononuclear cells (PBMCs) as well as 12 biochemical and clinical parameters of the study participants are significantly triggered by vitamin D(3). In this study, we performed a more focused selection of further 12 VDR target genes and demonstrated that changes of their mRNA expression in PBMCs of VitDmet subjects significantly correlate with alterations of 25-hydroxyvitamin D3 serum levels. Network and self-organizing map analysis of these datasets together with that of the other 24 parameters was followed by relevance calculations and identified changes in parathyroid hormone serum levels and the expression of the newly selected genes STS, BCL6, ITGAM, LRRC25, LPGAT1 and TREM1 as well as of the previously reported genes DUSP10 and CD14 as the most relevant parameters for describing vitamin D responsiveness in vivo. Moreover, parameter relevance ranking allowed the segregation of study subjects into high and low responders. Due to the long intervention period the vitamin D response was not too prominent on the level of transcriptional activation. Therefore, we performed in the separate VitDbol trial a short-term but high dose stimulation with a vitamin D3 bolus. In PBMCs of VitDbol subjects we observed direct transcriptional effects on the selected VDR target genes, such as an up to 2.1-fold increase already one day after supplementation onset. In conclusion, both long-term and short-term vitamin D(3) supplementation studies allow monitoring the vitamin D responsiveness of human individuals and represent new types of human in vivo vitamin D(3) investigations. Public Library of Science 2015-04-13 /pmc/articles/PMC4395145/ /pubmed/25875760 http://dx.doi.org/10.1371/journal.pone.0124339 Text en © 2015 Vukić et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Vukić, Maja
Neme, Antonio
Seuter, Sabine
Saksa, Noora
de Mello, Vanessa D. F.
Nurmi, Tarja
Uusitupa, Matti
Tuomainen, Tomi-Pekka
Virtanen, Jyrki K.
Carlberg, Carsten
Relevance of Vitamin D Receptor Target Genes for Monitoring the Vitamin D Responsiveness of Primary Human Cells
title Relevance of Vitamin D Receptor Target Genes for Monitoring the Vitamin D Responsiveness of Primary Human Cells
title_full Relevance of Vitamin D Receptor Target Genes for Monitoring the Vitamin D Responsiveness of Primary Human Cells
title_fullStr Relevance of Vitamin D Receptor Target Genes for Monitoring the Vitamin D Responsiveness of Primary Human Cells
title_full_unstemmed Relevance of Vitamin D Receptor Target Genes for Monitoring the Vitamin D Responsiveness of Primary Human Cells
title_short Relevance of Vitamin D Receptor Target Genes for Monitoring the Vitamin D Responsiveness of Primary Human Cells
title_sort relevance of vitamin d receptor target genes for monitoring the vitamin d responsiveness of primary human cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4395145/
https://www.ncbi.nlm.nih.gov/pubmed/25875760
http://dx.doi.org/10.1371/journal.pone.0124339
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