Vitamin D stimulates miR-26b-5p to inhibit placental COX-2 expression in preeclampsia.
Vitamin D stimulates miR-26b-5p to inhibit placental COX-2 expression in preeclampsia.
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DOI：
10.1038/s41598-021-90605-9
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发表时间：
2021-05-27
影响因子：
4.6
通讯作者：
Zhu H
中科院分区：
文献类型：
--
作者：
Cao Y;Jia X;Huang Y;Wang J;Lu C;Yuan X;Xu J;Zhu H
怀孕期间维生素D不足或缺乏与子痫前期风险增加有关。胎盘环氧化酶-2 （COX-2）活性的增加被认为有助于子痫前期的炎症反应。本研究旨在探讨维生素D是否能通过抑制胎盘COX-2的表达而使子痫前期受益。从40名孕妇（23名血压正常，17名子痫前期）获得胎盘组织。采用定量PCR检测miR-26b-5p的表达。免疫染色和Western blot检测维生素D受体（VDR）和COX-2的表达。体外培养HTR-8/SVneo滋养细胞，观察维生素D对氧化应激诱导剂CoCl2处理胎盘滋养细胞的抗炎作用。1,25(OH)2D3被用作生物活性维生素d。我们的研究结果显示，与血压正常的孕妇相比，子痫前期妇女胎盘中VDR和miR-26b-5p的表达降低，COX-2的表达增加。miR-26b-5p的短暂过表达减弱了CoCl2诱导的胎盘滋养细胞中COX-2表达上调和前列腺素E2 （PGE2）产生。1,25(OH)2D3处理可抑制cocl2诱导的胎盘滋养细胞中COX-2的上调。此外，miR-26b-5p的表达在1,25(OH)2D3处理的细胞中显著上调，而在VDR siRNA转染的细胞中则没有上调。总之，VDR和miR-26b-5p表达的下调与子痫前期妇女胎盘中COX-2表达的上调有关。1,25(OH)2D3可以促进miR-26b-5p的表达，从而抑制胎盘滋养细胞中COX-2的表达和PGE2的形成。维生素D通过促进VDR/miR-26b-5p表达而具有抗炎特性，这一发现为维生素D/VDR信号下调可能导致子痫前期炎症反应增加提供了重要证据。
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.
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