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.
Highlights
Vitamin D insufficiency or deficiency during pregnancy has been associated with an increased risk of preeclampsia
The exaggerated maternal inflammatory response in preeclampsia is attributed to the hypoxic placenta which is associated with abnormal production of c ytokines7, debris[8], and p rostaglandins[9], such as thromboxane ( TXA2) and prostacyclin (PGI2), by placental trophoblast cells. TXA2 is a potent vasoconstrictor, while PGI2 is a vasodilator
To determine if reduced miR-26b-5p expression contributes to the activated COX-2/prostaglandins system that are relevant to preeclampsia, we examined the role of miR-26b-5p in the oxidative stress-induced inflammatory response
Summary
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. 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. Downregulation of VDR and miR-26b-5p expression was associated with upregulation of COX-2 expression in the placentas from women with preeclampsia. Preeclampsia is a placentally induced disorder of p regnancy[6] According to this theory, the exaggerated maternal inflammatory response in preeclampsia is attributed to the hypoxic placenta which is associated with abnormal production of c ytokines7, debris[8], and p rostaglandins[9], such as thromboxane ( TXA2) and prostacyclin (PGI2), by placental trophoblast cells. Inhibition of COX-2/ PGE2 signaling might be beneficial in this disease
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