Vitamin D stimulates miR-26b-5p to inhibit placental COX-2 expression in preeclampsia
Yang Cao, Xiaotong Jia, Yujia Huang, Jiao Wang, Chunmei Lu, Xiaolei Yuan, Jie Xu, Hui Zhu
Abstract
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 CoCl 2 . 1,25(OH) 2 D 3 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 2 (PGE 2 ) production induced by CoCl 2 in placental trophoblasts. 1,25(OH) 2 D 3 treatment inhibited CoCl 2 -induced upregulation of COX-2 in placental trophoblasts. Moreover, miR-26b-5p expression were significantly upregulated in cells treated with 1,25(OH) 2 D 3 , 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) 2 D 3 could promote miR-26b-5p expression which in turn inhibited COX-2 expression and PGE 2 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.