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Transcriptomic Response to 1,25-Dihydroxyvitamin D in Human Fibroblasts with or without a Functional Vitamin D Receptor (VDR): Novel Target Genes and Insights into VDR Basal Transcriptional Activity

The vitamin D receptor (VDR) mediates vitamin D actions beyond bone health. While VDR activation by 1,25-dihydroxyvitamin D (1,25D) leads to robust transcriptional regulation, less is known about VDR actions in the absence of 1,25D. We analyzed the transcriptomic response to 1,25D in fibroblasts bea...

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Autores principales: Costa, Pedro L. F., França, Monica M., Katayama, Maria L., Carneiro, Eduardo T., Martin, Regina M., Folgueira, Maria A. K., Latronico, Ana C., Ferraz-de-Souza, Bruno
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523947/
https://www.ncbi.nlm.nih.gov/pubmed/30959822
http://dx.doi.org/10.3390/cells8040318
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author Costa, Pedro L. F.
França, Monica M.
Katayama, Maria L.
Carneiro, Eduardo T.
Martin, Regina M.
Folgueira, Maria A. K.
Latronico, Ana C.
Ferraz-de-Souza, Bruno
author_facet Costa, Pedro L. F.
França, Monica M.
Katayama, Maria L.
Carneiro, Eduardo T.
Martin, Regina M.
Folgueira, Maria A. K.
Latronico, Ana C.
Ferraz-de-Souza, Bruno
author_sort Costa, Pedro L. F.
collection PubMed
description The vitamin D receptor (VDR) mediates vitamin D actions beyond bone health. While VDR activation by 1,25-dihydroxyvitamin D (1,25D) leads to robust transcriptional regulation, less is known about VDR actions in the absence of 1,25D. We analyzed the transcriptomic response to 1,25D in fibroblasts bearing a severe homozygous hereditary vitamin D resistant rickets-related p.Arg30* VDR mutation (MUT) and in control fibroblasts (CO). Roughly 4.5% of the transcriptome was regulated by 1,25D in CO fibroblasts, while MUT cells without a functional VDR were insensitive to 1,25D. Novel VDR target genes identified in human fibroblasts included bone and cartilage factors CILP, EFNB2, and GALNT12. Vehicle-treated CO and MUT fibroblasts had strikingly different transcriptomes, suggesting basal VDR activity. Indeed, oppositional transcriptional effects in basal conditions versus after 1,25D activation were implied for a subset of target genes mostly involved with cell cycle. Cell proliferation assays corroborated this conjectured oppositional basal VDR activity, indicating that precise 1,25D dosage in target tissues might be essential for modulating vitamin D actions in human health.
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spelling pubmed-65239472019-06-03 Transcriptomic Response to 1,25-Dihydroxyvitamin D in Human Fibroblasts with or without a Functional Vitamin D Receptor (VDR): Novel Target Genes and Insights into VDR Basal Transcriptional Activity Costa, Pedro L. F. França, Monica M. Katayama, Maria L. Carneiro, Eduardo T. Martin, Regina M. Folgueira, Maria A. K. Latronico, Ana C. Ferraz-de-Souza, Bruno Cells Article The vitamin D receptor (VDR) mediates vitamin D actions beyond bone health. While VDR activation by 1,25-dihydroxyvitamin D (1,25D) leads to robust transcriptional regulation, less is known about VDR actions in the absence of 1,25D. We analyzed the transcriptomic response to 1,25D in fibroblasts bearing a severe homozygous hereditary vitamin D resistant rickets-related p.Arg30* VDR mutation (MUT) and in control fibroblasts (CO). Roughly 4.5% of the transcriptome was regulated by 1,25D in CO fibroblasts, while MUT cells without a functional VDR were insensitive to 1,25D. Novel VDR target genes identified in human fibroblasts included bone and cartilage factors CILP, EFNB2, and GALNT12. Vehicle-treated CO and MUT fibroblasts had strikingly different transcriptomes, suggesting basal VDR activity. Indeed, oppositional transcriptional effects in basal conditions versus after 1,25D activation were implied for a subset of target genes mostly involved with cell cycle. Cell proliferation assays corroborated this conjectured oppositional basal VDR activity, indicating that precise 1,25D dosage in target tissues might be essential for modulating vitamin D actions in human health. MDPI 2019-04-05 /pmc/articles/PMC6523947/ /pubmed/30959822 http://dx.doi.org/10.3390/cells8040318 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Costa, Pedro L. F.
França, Monica M.
Katayama, Maria L.
Carneiro, Eduardo T.
Martin, Regina M.
Folgueira, Maria A. K.
Latronico, Ana C.
Ferraz-de-Souza, Bruno
Transcriptomic Response to 1,25-Dihydroxyvitamin D in Human Fibroblasts with or without a Functional Vitamin D Receptor (VDR): Novel Target Genes and Insights into VDR Basal Transcriptional Activity
title Transcriptomic Response to 1,25-Dihydroxyvitamin D in Human Fibroblasts with or without a Functional Vitamin D Receptor (VDR): Novel Target Genes and Insights into VDR Basal Transcriptional Activity
title_full Transcriptomic Response to 1,25-Dihydroxyvitamin D in Human Fibroblasts with or without a Functional Vitamin D Receptor (VDR): Novel Target Genes and Insights into VDR Basal Transcriptional Activity
title_fullStr Transcriptomic Response to 1,25-Dihydroxyvitamin D in Human Fibroblasts with or without a Functional Vitamin D Receptor (VDR): Novel Target Genes and Insights into VDR Basal Transcriptional Activity
title_full_unstemmed Transcriptomic Response to 1,25-Dihydroxyvitamin D in Human Fibroblasts with or without a Functional Vitamin D Receptor (VDR): Novel Target Genes and Insights into VDR Basal Transcriptional Activity
title_short Transcriptomic Response to 1,25-Dihydroxyvitamin D in Human Fibroblasts with or without a Functional Vitamin D Receptor (VDR): Novel Target Genes and Insights into VDR Basal Transcriptional Activity
title_sort transcriptomic response to 1,25-dihydroxyvitamin d in human fibroblasts with or without a functional vitamin d receptor (vdr): novel target genes and insights into vdr basal transcriptional activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523947/
https://www.ncbi.nlm.nih.gov/pubmed/30959822
http://dx.doi.org/10.3390/cells8040318
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