Preeclampsia leads to dysregulation of various signaling pathways in placenta
Preeclampsia leads to dysregulation of various signaling pathways in placenta
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DOI：
10.1097/hjh.0b013e328344a82c
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发表时间：
2011-05-01
影响因子：
4.9
通讯作者：
Cha, Dong Hyun
中科院分区：
文献类型：
--
作者：
Kang, Jin Hee;Song, Haengseok;Cha, Dong Hyun
目的比较子痫前期患者和正常妊娠患者胎盘的基因表达谱。研究设计采用基因芯片技术分析10例子痫前期孕妇胎盘和10例非并发症妊娠(CON)患者胎盘的全基因组表达谱，明确子痫前期异常信号转导途径和基因表达谱。结果无监督的系统聚类法显示子痫前期在分子水平上具有异质性，而子痫前期组织的表达谱明显不同于正常子痫前期组织。一系列在子痫前期和CON之间差异表达的基因包括众所周知的子痫前期标志物，如Flt-1、Leptin、HTRA1和SIGLEC6。基因集浓缩分析是一种面向途径的表达谱分析方法，它提供的证据表明，许多生物学活性，包括调节肌动蛋白细胞骨架、转化生长因子β信号转导、氧化磷酸化和蛋白酶体活性的途径，在先兆子痫中异常上调或下调。通过RT-PCR和实时定量RT-PCR检测CON和子痫前期致病基因，进一步证实子痫前期患者的这些生物学过程存在系统性失调。结论子痫前期患者全基因组表达谱在分子水平上表现出异质性特征。基因和生物通路的失调可能导致先兆子痫失语的异常行为。我们的结果将有助于进一步了解子痫前期影响胎盘生理的潜在机制。J Hyperten 29：928-936(C)2011 Wolters Kluwer Health垂直酒吧Lippincott Williams&Wilkins。
Objectives To compare gene expression profiles of placentas from preeclamptic and normal pregnancies.Study design We performed microarray experiments to analyze genome-wide expression profiling for 10 placentas from pregnant women with preeclampsia and 10 placentas from women who experienced noncomplicated pregnancies (CON), and to identify dysregulated signaling pathways as well as genes in preeclampsia. RT-PCR, real-time RT-PCR and/or immunofluorescence analyses were performed to validate the data obtained from microarray experiments.Results Unsupervised hierarchical clustering showed heterogeneity of preeclampsia at the molecular levels, whereas expression profiles of preeclampsia are distinctly different from those of CON. A list of genes which are differentially expressed between preeclampsia and CON included well known preeclampsia markers, such as Flt-1, leptin, HTRA1 and SIGLEC6. Gene Set Enrichment Analysis, a pathway-oriented analysis method for expression profiles, provided evidence that a number of biological activities including pathways that regulate actin cytoskeleton, TGF beta signaling, oxidative phosphorylation, and proteasome activity were aberrantly either up-regulated or down-regulated in preeclampsia. RT-PCR and real-time-RT-PCR for genes contributing these biological pathways (gene sets) enriched in either CON or preeclampsia reinforced that these biological processes were systemically dysregulated in preeclampsia.Conclusions Genome-wide expression profiles of preeclampsia showed heterogeneous characteristics of preeclampsia at the molecular levels. Dysregulation of genes and biological pathways could contribute to abnormal behavior of preeclmapsia. Our results will help further understand underlying mechanisms by which preeclampsia affects placental physiology. J Hypertens 29: 928-936 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.