Vitamin D stimulates miR-26b-5p to inhibit placental COX-2 expression in preeclampsia

Abstract Vitamin D insufficiency or deficiency during pregnancy has been associated with an increased risk of preeclampsia. Increased placental cyclooxygenase-2 (COX-2) activity was proposed to contribute to the inflammatory response in preeclampsia. This study was to investigate if vitamin D can be...

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Autores principales: Yang Cao, Xiaotong Jia, Yujia Huang, Jiao Wang, Chunmei Lu, Xiaolei Yuan, Jie Xu, Hui Zhu
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:45def7adeb594b32a74966974aefbca72021-12-02T15:00:39ZVitamin D stimulates miR-26b-5p to inhibit placental COX-2 expression in preeclampsia10.1038/s41598-021-90605-92045-2322https://doaj.org/article/45def7adeb594b32a74966974aefbca72021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90605-9https://doaj.org/toc/2045-2322Abstract Vitamin D insufficiency or deficiency during pregnancy has been associated with an increased risk of preeclampsia. Increased placental cyclooxygenase-2 (COX-2) activity was proposed to contribute to the inflammatory response in preeclampsia. This study was to investigate if vitamin D can benefit preeclampsia by inhibiting placental COX-2 expression. Placenta tissues were obtained from 40 pregnant women (23 normotensive and 17 preeclampsia). miR-26b-5p expression was assessed by quantitative PCR. Vitamin D receptor (VDR) expression and COX-2 expression were determined by immunostaining and Western blot. HTR-8/SVneo trophoblastic cells were cultured in vitro to test anti-inflammatory effects of vitamin D in placental trophoblasts treated with oxidative stress inducer CoCl2. 1,25(OH)2D3 was used as bioactive vitamin D. Our results showed that reduced VDR and miR-26b-5p expression, but increased COX-2 expression, was observed in the placentas from women with preeclampsia compared to those from normotensive pregnant women. Transient overexpression of miR-26b-5p attenuated the upregulation of COX-2 expression and prostaglandin E2 (PGE2) production induced by CoCl2 in placental trophoblasts. 1,25(OH)2D3 treatment inhibited CoCl2-induced upregulation of COX-2 in placental trophoblasts. Moreover, miR-26b-5p expression were significantly upregulated in cells treated with 1,25(OH)2D3, but not in cells transfected with VDR siRNA. Conclusively, downregulation of VDR and miR-26b-5p expression was associated with upregulation of COX-2 expression in the placentas from women with preeclampsia. 1,25(OH)2D3 could promote miR-26b-5p expression which in turn inhibited COX-2 expression and PGE2 formation in placental trophoblasts. The finding of anti-inflammatory property by vitamin D through promotion of VDR/miR-26b-5p expression provides significant evidence that downregulation of vitamin D/VDR signaling could contribute to increased inflammatory response in preeclampsia.Yang CaoXiaotong JiaYujia HuangJiao WangChunmei LuXiaolei YuanJie XuHui ZhuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yang Cao
Xiaotong Jia
Yujia Huang
Jiao Wang
Chunmei Lu
Xiaolei Yuan
Jie Xu
Hui Zhu
Vitamin D stimulates miR-26b-5p to inhibit placental COX-2 expression in preeclampsia
description Abstract Vitamin D insufficiency or deficiency during pregnancy has been associated with an increased risk of preeclampsia. Increased placental cyclooxygenase-2 (COX-2) activity was proposed to contribute to the inflammatory response in preeclampsia. This study was to investigate if vitamin D can benefit preeclampsia by inhibiting placental COX-2 expression. Placenta tissues were obtained from 40 pregnant women (23 normotensive and 17 preeclampsia). miR-26b-5p expression was assessed by quantitative PCR. Vitamin D receptor (VDR) expression and COX-2 expression were determined by immunostaining and Western blot. HTR-8/SVneo trophoblastic cells were cultured in vitro to test anti-inflammatory effects of vitamin D in placental trophoblasts treated with oxidative stress inducer CoCl2. 1,25(OH)2D3 was used as bioactive vitamin D. Our results showed that reduced VDR and miR-26b-5p expression, but increased COX-2 expression, was observed in the placentas from women with preeclampsia compared to those from normotensive pregnant women. Transient overexpression of miR-26b-5p attenuated the upregulation of COX-2 expression and prostaglandin E2 (PGE2) production induced by CoCl2 in placental trophoblasts. 1,25(OH)2D3 treatment inhibited CoCl2-induced upregulation of COX-2 in placental trophoblasts. Moreover, miR-26b-5p expression were significantly upregulated in cells treated with 1,25(OH)2D3, but not in cells transfected with VDR siRNA. Conclusively, downregulation of VDR and miR-26b-5p expression was associated with upregulation of COX-2 expression in the placentas from women with preeclampsia. 1,25(OH)2D3 could promote miR-26b-5p expression which in turn inhibited COX-2 expression and PGE2 formation in placental trophoblasts. The finding of anti-inflammatory property by vitamin D through promotion of VDR/miR-26b-5p expression provides significant evidence that downregulation of vitamin D/VDR signaling could contribute to increased inflammatory response in preeclampsia.
format article
author Yang Cao
Xiaotong Jia
Yujia Huang
Jiao Wang
Chunmei Lu
Xiaolei Yuan
Jie Xu
Hui Zhu
author_facet Yang Cao
Xiaotong Jia
Yujia Huang
Jiao Wang
Chunmei Lu
Xiaolei Yuan
Jie Xu
Hui Zhu
author_sort Yang Cao
title Vitamin D stimulates miR-26b-5p to inhibit placental COX-2 expression in preeclampsia
title_short Vitamin D stimulates miR-26b-5p to inhibit placental COX-2 expression in preeclampsia
title_full Vitamin D stimulates miR-26b-5p to inhibit placental COX-2 expression in preeclampsia
title_fullStr Vitamin D stimulates miR-26b-5p to inhibit placental COX-2 expression in preeclampsia
title_full_unstemmed Vitamin D stimulates miR-26b-5p to inhibit placental COX-2 expression in preeclampsia
title_sort vitamin d stimulates mir-26b-5p to inhibit placental cox-2 expression in preeclampsia
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/45def7adeb594b32a74966974aefbca7
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