Jie Xu1,2, Yang Gu1, David F Lewis1, Danielle B Cooper1, Charles E McCathran1, Yuping Wang1. 1. Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center - Shreveport, Shreveport, LA, USA. 2. Department of Physiology, Harbin Medical University, Harbin, China.
Abstract
PROBLEM: To investigate whether downregulation of miR-126-3p and vitamin D receptor (VDR) expression contributes to increased endothelial inflammatory response in preeclampsia. METHODS OF STUDY: Maternal vessel miR-126-3p expression was assessed by in situ hybridization. VDR expression and VCAM-1 expression were determined by immunostaining. Subcutaneous adipose tissue sections from normotensive and preeclamptic pregnant women were used. HUVECs from normotensive deliveries were used to test anti-inflammatory effects of vitamin D and miR-126-3p in endothelial cells (ECs) treated with TNFα in vitro. 1,25(OH)2 D3 was used as bioactive vitamin D. Transient overexpression of miR-126-3p in ECs was induced by transfection of pre-mir-126 precursor. Endothelial VCAM-1 and SOCS-3 expression or production was determined by Western blotting or by ELISA, respectively. RESULTS: Reduced VDR and miR-126-3p expression, but increased VCAM-1 expression, was observed in maternal vessel endothelium in tissue sections from women with preeclampsia compared to normotensive pregnant controls. Transient overexpression of miR-126-3p not only attenuated upregulation of VCAM-1 expression and production, but also preserved downregulation of SOCS-3 expression, induced by TNFα in ECs. VDR expression and miR-126-3p expression were significantly upregulated in cells treated with 1,25(OH)2 D3 , but not in cells transfected with VDR siRNA. CONCLUSION: Downregulation of VDR and miR-126-3p expression was associated with upregulation of VCAM-1 expression in systemic vessel endothelium in preeclampsia. The finding of increased anti-inflammatory property by 1,25(OH)2 D3 through promotion of VDR and miR-126-3p expression in ECs provide plausible evidence that vitamin D deficiency and downregulation of VDR expression could contribute to increased inflammatory phenotypic changes in maternal vasculature in preeclampsia.
PROBLEM: To investigate whether downregulation of miR-126-3p and vitamin D receptor (VDR) expression contributes to increased endothelial inflammatory response in preeclampsia. METHODS OF STUDY: Maternal vessel miR-126-3p expression was assessed by in situ hybridization. VDR expression and VCAM-1 expression were determined by immunostaining. Subcutaneous adipose tissue sections from normotensive and preeclamptic pregnant women were used. HUVECs from normotensive deliveries were used to test anti-inflammatory effects of vitamin D and miR-126-3p in endothelial cells (ECs) treated with TNFα in vitro. 1,25(OH)2 D3 was used as bioactive vitamin D. Transient overexpression of miR-126-3p in ECs was induced by transfection of pre-mir-126 precursor. Endothelial VCAM-1 and SOCS-3 expression or production was determined by Western blotting or by ELISA, respectively. RESULTS: Reduced VDR and miR-126-3p expression, but increased VCAM-1 expression, was observed in maternal vessel endothelium in tissue sections from women with preeclampsia compared to normotensive pregnant controls. Transient overexpression of miR-126-3p not only attenuated upregulation of VCAM-1 expression and production, but also preserved downregulation of SOCS-3 expression, induced by TNFα in ECs. VDR expression and miR-126-3p expression were significantly upregulated in cells treated with 1,25(OH)2 D3 , but not in cells transfected with VDR siRNA. CONCLUSION: Downregulation of VDR and miR-126-3p expression was associated with upregulation of VCAM-1 expression in systemic vessel endothelium in preeclampsia. The finding of increased anti-inflammatory property by 1,25(OH)2 D3 through promotion of VDR and miR-126-3p expression in ECs provide plausible evidence that vitamin D deficiency and downregulation of VDR expression could contribute to increased inflammatory phenotypic changes in maternal vasculature in preeclampsia.