Department of Physiology, Harbin Medical University, Harbin, 150081, China.
Department of Obstetrics and Gynecology, Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.
Sci Rep. 2021 May 27;11(1):11168. doi: 10.1038/s41598-021-90605-9.
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 CoCl. 1,25(OH)D 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 E (PGE) production induced by CoCl in placental trophoblasts. 1,25(OH)D treatment inhibited CoCl-induced upregulation of COX-2 in placental trophoblasts. Moreover, miR-26b-5p expression were significantly upregulated in cells treated with 1,25(OH)D, 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)D could promote miR-26b-5p expression which in turn inhibited COX-2 expression and PGE 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.
维生素 D 不足或缺乏与子痫前期风险增加有关。研究表明，胎盘环氧化酶-2（COX-2）活性增加可能导致子痫前期的炎症反应。本研究旨在探讨维生素 D 是否可以通过抑制胎盘 COX-2 表达来改善子痫前期。收集 40 名孕妇（23 名正常血压孕妇和 17 名子痫前期孕妇）胎盘组织。采用 qPCR 检测 miR-26b-5p 表达。免疫染色和 Western blot 检测维生素 D 受体（VDR）和 COX-2 表达。体外培养 HTR-8/SVneo 滋养层细胞，用氧化应激诱导剂 CoCl 处理胎盘滋养层细胞，检测维生素 D 的抗炎作用。1,25（OH）2D 作为生物活性维生素 D。结果显示，与正常血压孕妇相比，子痫前期孕妇胎盘组织中 VDR 和 miR-26b-5p 表达降低，COX-2 表达升高。瞬时过表达 miR-26b-5p 可减弱 CoCl 诱导的胎盘滋养层细胞 COX-2 表达和前列腺素 E（PGE）的产生。1,25（OH）2D 处理抑制了 CoCl 诱导的胎盘滋养层细胞 COX-2 的上调。此外，1,25（OH）2D 处理可显著上调细胞中 miR-26b-5p 的表达，但不能上调转染 VDR siRNA 的细胞中 miR-26b-5p 的表达。结论：子痫前期孕妇胎盘组织中 VDR 和 miR-26b-5p 表达下调与 COX-2 表达上调有关。1,25（OH）2D 可促进 miR-26b-5p 表达，进而抑制胎盘滋养层细胞 COX-2 表达和 PGE 形成。维生素 D 通过促进 VDR/miR-26b-5p 表达发挥抗炎作用的发现为维生素 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。
