Shao Jun, Zhao Mingzhi, Tong Mancy, Wei Jia, Wise Michelle R, Stone Peter, Chamley Lawrence, Chen Qi
The Hospital of Obstetrics & GynaecologyFudan University, China.
Department of Obstetrics & GynaecologyThe University of Auckland, New Zealand.
Reproduction. 2016 Dec;152(6):775-784. doi: 10.1530/REP-16-0083. Epub 2016 Sep 22.
Preeclampsia is triggered by an as yet unknown toxin from the placenta. Antiphospholipid antibodies (aPL), a strong risk factor for preeclampsia, have been shown to induce the production of toxic trophoblastic debris from the placenta. High mobility group box 1 (HMGB1) is a proinflammatory danger signal, and the expression of it has been reported to be increased in preeclampsia. This study examined whether aPL or preeclamptic sera increase the expression of HMGB1 in the syncytiotrophoblast or trophoblastic debris. Trophoblastic debris from normal placental explants that had been cultured with aPL or preeclamptic sera was exposed to endothelial cells. Endothelial cell activation was quantified by cell-surface ICAM-1 expression and U937 monocyte adhesion. The expression of HMGB1 in placental explants and trophoblastic debris that had been treated with aPL or preeclamptic sera was measured by immunohistochemistry and western blotting. The expression of the receptor for advanced glycation end products (RAGE) in endothelial cells was quantified by western blotting. Compared with controls, the expression of HMGB1 in the cytoplasm of the syncytiotrophoblast and trophoblastic debris was increased by treating placental explants with aPL or preeclamptic sera. The increased levels of HMGB1 contributed to endothelial cell activation, mediated in part by the RAGE. Preeclamptic sera and aPL both induced an increase in the cytoplasmic levels of the danger signal HMGB1 in trophoblastic debris. This increased HMGB1 in trophoblastic debris may be one of the toxic factors released from the placenta in preeclampsia.
子痫前期由胎盘产生的一种未知毒素引发。抗磷脂抗体（aPL）是子痫前期的一个强风险因素，已被证明可诱导胎盘产生有毒的滋养层碎片。高迁移率族蛋白B1（HMGB1）是一种促炎危险信号，据报道其在子痫前期中的表达会增加。本研究检测了aPL或子痫前期血清是否会增加合体滋养层细胞或滋养层碎片中HMGB1的表达。将用aPL或子痫前期血清培养的正常胎盘外植体产生的滋养层碎片暴露于内皮细胞。通过细胞表面ICAM-1表达和U937单核细胞黏附来定量内皮细胞活化。通过免疫组织化学和蛋白质印迹法测量用aPL或子痫前期血清处理的胎盘外植体和滋养层碎片中HMGB1的表达。通过蛋白质印迹法定量内皮细胞中晚期糖基化终产物受体（RAGE）的表达。与对照组相比，用aPL或子痫前期血清处理胎盘外植体可增加合体滋养层细胞和滋养层碎片细胞质中HMGB1的表达。HMGB1水平的升高促成了内皮细胞活化，部分是由RAGE介导的。子痫前期血清和aPL均诱导滋养层碎片中危险信号HMGB1的细胞质水平升高。滋养层碎片中这种升高的HMGB1可能是子痫前期胎盘释放的有毒因子之一。
