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Vitamin D stimulates multiple microRNAs to inhibit CRH and other pro-labor genes in human placenta

Maternal vitamin D deficiency is linked to adverse pregnancy outcomes including spontaneous preterm birth (SPB). Placental corticotropin-releasing hormone (CRH) has been proposed to be part of a clock that governs the length of gestation in humans, with elevated maternal serum levels predicting earl...

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Autores principales: Wang, Bingbing, Cruz Ithier, Mayra, Parobchak, Nataliya, Yadava, Stacy M, Schulkin, Jay, Rosen, Todd
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280586/
https://www.ncbi.nlm.nih.gov/pubmed/30395535
http://dx.doi.org/10.1530/EC-18-0345
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author Wang, Bingbing
Cruz Ithier, Mayra
Parobchak, Nataliya
Yadava, Stacy M
Schulkin, Jay
Rosen, Todd
author_facet Wang, Bingbing
Cruz Ithier, Mayra
Parobchak, Nataliya
Yadava, Stacy M
Schulkin, Jay
Rosen, Todd
author_sort Wang, Bingbing
collection PubMed
description Maternal vitamin D deficiency is linked to adverse pregnancy outcomes including spontaneous preterm birth (SPB). Placental corticotropin-releasing hormone (CRH) has been proposed to be part of a clock that governs the length of gestation in humans, with elevated maternal serum levels predicting early delivery. In this study, we test the hypothesis that vitamin D could contribute to the prevention of preterm labor by inhibiting CRH and other pro-labor mediators. The biological activity of vitamin D occurs via two pathways: non-genomic and genomic responses, both of which involve binding of 1,25-dihydroxyvitamin D (1,25(OH)2D), the active metabolite of vitamin D binding to the vitamin D receptor (VDR). By using chromatin immunoprecipitation followed by sequencing (ChIP-seq), we found that 1,25(OH)2D stimulates association of VDR with a number of miRNA genes including MIR181B2 and MIR26B, and their mature products miR-181b-5p and miR-26b-5p are predicted to target CRH and cyclooxygenase-2 (COX-2) mRNA at 3′-untranslated region (UTR), respectively. We performed RT-qPCR analysis to validate that expression of mature miR-181b-5p and miR-26b-5p in term human syncytiotrophoblast increased in response to treatment with 1,25(OH)2D. miR-181b-5p- or miR-26b-5p-mediated inhibition of CRH or COX-2 was further assessed by the use of miRNA mimics/inhibitors and a luciferase reporter assay. Taken together, this study has identified novel mechanisms by which vitamin D downregulates pro-labor genes and could lower the risk of preterm delivery.
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spelling pubmed-62805862018-12-10 Vitamin D stimulates multiple microRNAs to inhibit CRH and other pro-labor genes in human placenta Wang, Bingbing Cruz Ithier, Mayra Parobchak, Nataliya Yadava, Stacy M Schulkin, Jay Rosen, Todd Endocr Connect Research Maternal vitamin D deficiency is linked to adverse pregnancy outcomes including spontaneous preterm birth (SPB). Placental corticotropin-releasing hormone (CRH) has been proposed to be part of a clock that governs the length of gestation in humans, with elevated maternal serum levels predicting early delivery. In this study, we test the hypothesis that vitamin D could contribute to the prevention of preterm labor by inhibiting CRH and other pro-labor mediators. The biological activity of vitamin D occurs via two pathways: non-genomic and genomic responses, both of which involve binding of 1,25-dihydroxyvitamin D (1,25(OH)2D), the active metabolite of vitamin D binding to the vitamin D receptor (VDR). By using chromatin immunoprecipitation followed by sequencing (ChIP-seq), we found that 1,25(OH)2D stimulates association of VDR with a number of miRNA genes including MIR181B2 and MIR26B, and their mature products miR-181b-5p and miR-26b-5p are predicted to target CRH and cyclooxygenase-2 (COX-2) mRNA at 3′-untranslated region (UTR), respectively. We performed RT-qPCR analysis to validate that expression of mature miR-181b-5p and miR-26b-5p in term human syncytiotrophoblast increased in response to treatment with 1,25(OH)2D. miR-181b-5p- or miR-26b-5p-mediated inhibition of CRH or COX-2 was further assessed by the use of miRNA mimics/inhibitors and a luciferase reporter assay. Taken together, this study has identified novel mechanisms by which vitamin D downregulates pro-labor genes and could lower the risk of preterm delivery. Bioscientifica Ltd 2018-11-05 /pmc/articles/PMC6280586/ /pubmed/30395535 http://dx.doi.org/10.1530/EC-18-0345 Text en © 2018 The authors http://creativecommons.org/licenses/by-nc/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Research
Wang, Bingbing
Cruz Ithier, Mayra
Parobchak, Nataliya
Yadava, Stacy M
Schulkin, Jay
Rosen, Todd
Vitamin D stimulates multiple microRNAs to inhibit CRH and other pro-labor genes in human placenta
title Vitamin D stimulates multiple microRNAs to inhibit CRH and other pro-labor genes in human placenta
title_full Vitamin D stimulates multiple microRNAs to inhibit CRH and other pro-labor genes in human placenta
title_fullStr Vitamin D stimulates multiple microRNAs to inhibit CRH and other pro-labor genes in human placenta
title_full_unstemmed Vitamin D stimulates multiple microRNAs to inhibit CRH and other pro-labor genes in human placenta
title_short Vitamin D stimulates multiple microRNAs to inhibit CRH and other pro-labor genes in human placenta
title_sort vitamin d stimulates multiple micrornas to inhibit crh and other pro-labor genes in human placenta
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280586/
https://www.ncbi.nlm.nih.gov/pubmed/30395535
http://dx.doi.org/10.1530/EC-18-0345
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