Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center - Shreveport, Shreveport, LA, USA.
Department of Physiology, Harbin Medical University, Harbin, China.
Am J Reprod Immunol. 2019 Oct;82(4):e13172. doi: 10.1111/aji.13172. Epub 2019 Aug 17.
To investigate whether downregulation of miR-126-3p and vitamin D receptor (VDR) expression contributes to increased endothelial inflammatory response in preeclampsia.
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) D 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.
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) D , but not in cells transfected with VDR siRNA.
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) D 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.
研究 miR-126-3p 和维生素 D 受体 (VDR) 表达下调是否导致子痫前期内皮炎症反应增加。
通过原位杂交评估母体血管 miR-126-3p 的表达。通过免疫染色测定 VDR 表达和 VCAM-1 表达。使用来自正常血压和子痫前期孕妇的皮下脂肪组织切片。使用来自正常分娩的 HUVEC 来测试维生素 D 和 miR-126-3p 在体外用 TNFα 处理的内皮细胞 (EC) 中的抗炎作用。1,25(OH)2D 用作生物活性维生素 D。通过转染前 miR-126 前体诱导 EC 中 miR-126-3p 的瞬时过表达。通过 Western 印迹或 ELISA 分别测定内皮 VCAM-1 和 SOCS-3 的表达或产生。
与正常血压孕妇对照相比，子痫前期妇女组织切片中母体血管内皮中观察到 VDR 和 miR-126-3p 表达减少，而 VCAM-1 表达增加。miR-126-3p 的瞬时过表达不仅减弱了 TNFα 诱导的 EC 中 VCAM-1 表达和产生的上调，而且还保留了 SOCS-3 表达的下调。用 1,25(OH)2D 处理的细胞中 VDR 表达和 miR-126-3p 表达显著上调，但用 VDR siRNA 转染的细胞中则没有。
子痫前期全身血管内皮中 VDR 和 miR-126-3p 表达下调与 VCAM-1 表达上调有关。通过促进 VDR 和 miR-126-3p 在 EC 中的表达，1,25(OH)2D 增加抗炎特性的发现提供了合理的证据，表明维生素 D 缺乏和 VDR 表达下调可能导致子痫前期母体血管中炎症表型变化增加。
