Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary.
Virchows Arch. 2013 Sep;463(3):445-58. doi: 10.1007/s00428-013-1426-0. Epub 2013 Jun 27.
Preeclampsia is characterized by maternal systemic anti-angiogenic and pro-inflammatory states. Syndecan-1 is a cell surface proteoglycan expressed by the syncytiotrophoblast, which plays an important role in angiogenesis and resolution of inflammation. Our aim was to examine placental syndecan-1 expression in preeclampsia with or without hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Placentas were obtained from women in the following groups: (1) late-onset preeclampsia (n = 8); (2) early-onset preeclampsia without (n = 7) and (3) with HELLP syndrome (n = 8); (4) preterm controls (n = 5); and (5) term controls (n = 9). Tissue microarrays (TMAs) were constructed from paraffin-embedded placentas. TMA slides were immunostained for syndecan-1 and evaluated using microscopy, virtual microscopy, and semi-automated image analysis. Maternal sera from patients with preeclampsia (n = 49) and controls (n = 32) were immunoassayed for syndecan-1. BeWo cells were treated with Forskolin or Latrunculin B or kept in ischemic conditions. SDC1 expression and syndecan-1 production were investigated with qRT-PCR, confocal microscopy, and immunoassays. Syndecan-1 was localized to the syncytiotrophoblast apical membrane in normal placentas. Syndecan-1 immunoscores were higher in late-onset preeclampsia (p = 0.0001) and early-onset preeclampsia with or without HELLP syndrome (p = 0.02 for both) than in controls. Maternal serum syndecan-1 concentration was lower in preeclampsia (median, 673 ng/ml; interquartile range, 459-1,161 ng/ml) than in controls (1,158 ng/ml; 622-1,480 ng/ml). SDC1 expression and syndecan-1 immunostainings in BeWo cells and syndecan-1 concentrations in supernatants increased during cell differentiation. Disruption of the actin cytoskeleton with Latrunculin B decreased syndecan-1 release, while ischemic conditions increased it. Syncytiotrophoblastic syndecan-1 expression depends on the differentiation of villous trophoblasts, and trophoblastic syndecan-1 release is decreased in preeclampsia and HELLP syndrome. This phenomenon may be related to the disturbed syncytiotrophoblastic cortical actin cytoskeleton and associated with maternal anti-angiogenic and pro-inflammatory states in these syndromes.
子痫前期的特征是母体全身抗血管生成和促炎状态。硫酸乙酰肝素蛋白聚糖-1 是合体滋养层表达的细胞表面蛋白聚糖，在血管生成和炎症消退中发挥重要作用。我们的目的是检查无溶血、肝酶升高和血小板减少（HELLP）综合征的子痫前期患者的胎盘硫酸乙酰肝素蛋白聚糖-1 表达。从以下组别的女性中获得胎盘：（1）晚发型子痫前期（n = 8）；（2）无（n = 7）和（3）有 HELLP 综合征（n = 8）的早发型子痫前期；（4）早产对照组（n = 5）；和（5）足月对照组（n = 9）。从石蜡包埋的胎盘中构建组织微阵列（TMA）。用免疫组织化学法对 TMA 切片进行硫酸乙酰肝素蛋白聚糖-1 免疫染色，并通过显微镜、虚拟显微镜和半自动图像分析进行评估。用免疫分析法检测子痫前期患者（n = 49）和对照组（n = 32）的母体血清中的硫酸乙酰肝素蛋白聚糖-1。用 Forskolin 或 Latrunculin B 处理 BeWo 细胞或使其处于缺血状态。用 qRT-PCR、共聚焦显微镜和免疫测定法研究 SDC1 表达和硫酸乙酰肝素蛋白聚糖-1 的产生。硫酸乙酰肝素蛋白聚糖-1 在正常胎盘的合体滋养层顶膜上定位。晚发型子痫前期（p = 0.0001）和早发型子痫前期（无论有无 HELLP 综合征）的硫酸乙酰肝素蛋白聚糖-1 免疫评分均高于对照组（均为 p = 0.02）。子痫前期患者的母体血清硫酸乙酰肝素蛋白聚糖-1 浓度低于对照组（中位数为 673 ng/ml；四分位距为 459-1161 ng/ml）（1158 ng/ml；622-1480 ng/ml）。BeWo 细胞中的 SDC1 表达和硫酸乙酰肝素蛋白聚糖-1 免疫染色以及上清液中的硫酸乙酰肝素蛋白聚糖-1 浓度在细胞分化过程中增加。用 Latrunculin B 破坏细胞骨架肌动蛋白可减少硫酸乙酰肝素蛋白聚糖-1 的释放，而缺血条件则增加其释放。合胞滋养层硫酸乙酰肝素蛋白聚糖-1 的表达取决于绒毛滋养层的分化，子痫前期和 HELLP 综合征中合胞滋养层硫酸乙酰肝素蛋白聚糖-1 的释放减少。这种现象可能与合胞滋养层皮质肌动蛋白细胞骨架的紊乱有关，并与这些综合征中的母体抗血管生成和促炎状态有关。
