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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Bioscientifica Ltd
2018
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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. |
format | Online Article Text |
id | pubmed-6280586 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Bioscientifica Ltd |
record_format | MEDLINE/PubMed |
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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