Back to Search
Start Over
Relevance of vitamin D receptor target genes for monitoring the vitamin D responsiveness of primary human cells
- Source :
- PLoS ONE, Vol 10, Iss 4, p e0124339 (2015), PLoS ONE
- Publication Year :
- 2015
- Publisher :
- Public Library of Science (PLoS), 2015.
-
Abstract
- Article<br />Vitamin D3 has transcriptome- and genome-wide effects and activates, via the binding of its metabolite 1α,25-dihydroxyvitamin D3 to the transcription factor vitamin D receptor (VDR), several hundred target genes. Using samples from a 5-month vitamin D3 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 D3. 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 D3 supplementation studies allow monitoring the vitamin D responsiveness of human individuals and represent new types of human in vivo vitamin D3 investigations.<br />publisher version<br />http://purl.org/eprint/status/PeerReviewed
- Subjects :
- Male
Glucose tolerance tests
Parathyroid hormone
lcsh:Medicine
Calcitriol receptor
Transcriptome
chemistry.chemical_compound
0302 clinical medicine
Gene Regulatory Networks
Vitamin D
Receptor
lcsh:Science
0303 health sciences
Multidisciplinary
Vitamins
Middle Aged
3. Good health
Genetic networks
Multigene Family
030220 oncology & carcinogenesis
Female
Network analysis
Research Article
Signal Transduction
Vitamin
Chromatin Immunoprecipitation
medicine.medical_specialty
DNA transcription
Biology
Real-Time Polymerase Chain Reaction
vitamin D deficiency
03 medical and health sciences
In vivo
Internal medicine
medicine
Vitamin D and neurology
Humans
030304 developmental biology
lcsh:R
Vitamin D Deficiency
medicine.disease
Endocrinology
Gene Expression Regulation
chemistry
Dietary Supplements
Leukocytes, Mononuclear
Receptors, Calcitriol
lcsh:Q
Gene expression
Biomarkers
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 10
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....25ff41cd2aa6ff74384b979ed45416b6