合体滋养层微绒毛膜处理对人脐静脉内皮细胞基因表达的影响。

Effect of syncytiotrophoblast microvillous membrane treatment on gene expression in human umbilical vein endothelial cells.

作者信息

Hoegh A M, Tannetta D, Sargent I, Borup R, Nielsen F C, Redman C, Sørensen S, Hviid T V F

机构信息

Department of Clinical Biochemistry, Copenhagen University Hospital H:S Hvidovre Hospital, Hvidovre, Denmark.

出版信息

BJOG. 2006 Nov;113(11):1270-9. doi: 10.1111/j.1471-0528.2006.01061.x.

Abstract

OBJECTIVE

Syncytiotrophoblast membrane fragments (STBM) exist in the peripheral circulation in pregnant women and it has been shown that the level of circulating STBM is significantly increased with pre-eclampsia compared with uncomplicated pregnancies. STBM could be one of the factors which directly causes the endothelial cell dysfunction of pre-eclampsia. This study investigates the effect of STBM on endothelial cell gene expression.

DESIGN

Human umbilical vein endothelial cells were cultured in the presence and absence of STBM. At specified time points, total RNA was purified from the cultures and analysed on microarrays.

SETTING

A laboratory investigation using placentas obtained from a hospital delivery ward.

SAMPLE

Placentas from nine healthy women were obtained. STBM vesicles were isolated from the placentas and umbilical vein endothelial cell cultures were established from the umbilical cords.

METHODS

Gene expression was screened by Affymetrix GeneChips and confirmed with real-time polymerase chain reaction or enzyme-linked immunosorbent assay.

MAIN OUTCOME MEASURES

Fold changes in gene expression levels between treated and control cultures were calculated from the microarray results.

RESULTS

Overall, the results do not show any great changes in gene expression in endothelial cells after STBM treatment (28 genes changed two-fold or more out of approximately 10,000 genes examined by microarray). In general, the changes observed are consistent with inhibition of proliferation of endothelial cells by exposure to STBM. The unfolded protein response in particular may be involved.

CONCLUSIONS

STBM may influence endothelial cell function during pregnancy but STBM alone cannot account for the entire range of endothelial dysfunctions observed in pre-eclampsia.

摘要

目的

合体滋养层细胞膜碎片(STBM)存在于孕妇的外周循环中,并且已经表明,与未并发子痫前期的妊娠相比,子痫前期患者循环中的STBM水平显著升高。STBM可能是直接导致子痫前期内皮细胞功能障碍的因素之一。本研究调查了STBM对内皮细胞基因表达的影响。

设计

在有或无STBM的情况下培养人脐静脉内皮细胞。在特定时间点,从培养物中纯化总RNA并在微阵列上进行分析。

地点

使用从医院产房获得的胎盘进行实验室研究。

样本

获取了九名健康女性的胎盘。从胎盘中分离出STBM囊泡,并从脐带建立脐静脉内皮细胞培养物。

方法

通过Affymetrix基因芯片筛选基因表达,并用实时聚合酶链反应或酶联免疫吸附测定进行确认。

主要观察指标

根据微阵列结果计算处理组和对照组培养物之间基因表达水平的倍数变化。

结果

总体而言,STBM处理后内皮细胞的基因表达没有显示出任何重大变化(在通过微阵列检测的约10,000个基因中,有28个基因变化了两倍或更多)。一般来说,观察到的变化与暴露于STBM后内皮细胞增殖的抑制一致。特别是未折叠蛋白反应可能参与其中。

结论

STBM可能在妊娠期间影响内皮细胞功能,但单独的STBM不能解释子痫前期中观察到的全部内皮功能障碍。

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