首页> 美国卫生研究院文献>Molecular Human Reproduction >Gene expression profiling of placentae from women with early- and late-onset pre-eclampsia: down-regulation of the angiogenesis-related genes ACVRL1 and EGFL7 in early-onset disease
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Gene expression profiling of placentae from women with early- and late-onset pre-eclampsia: down-regulation of the angiogenesis-related genes ACVRL1 and EGFL7 in early-onset disease

机译:患有早发型和晚发型先兆子痫的女性胎盘的基因表达谱:在早发型疾病中血管生成相关基因ACVRL1和EGFL7的下调

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摘要

The underlying mechanisms behind the obstetric condition pre-eclampsia (PE) are still unclear. Manifestation of PE is heterogeneous and it has therefore been proposed to be a syndrome with different causes rather than one disease with a specific aetiology. Recently, we showed differences in circulating angiogenic factors between two subgroups—early- and late-onset PE. To further elucidate the differences between the two, we investigated placental gene expression profiles. Whole genome microarray technology and bioinformatic analysis were used to evaluate gene expression profiles in placentae from early- (24–32 gestational weeks, n = 8) and late-onset (36–41 gestational weeks, n = 7) PE. The results were verified by using quantitative real-time (qRT)–PCR. We found significant differences in the expression of 196 genes in early- compared with late-onset PE, 45 of these genes showing a fold change above 2. Bioinformatic analysis revealed alterations in angiogenesis and regulation of cell motility. Two angiogenesis-associated transcripts (Egfl7 and Acvrl1) showed lower expression in early-onset PE versus late-onset PE (P = 0.037 and P = 0.003) and versus gestational age-matched controls (P = 0.007 and P = 0.011). We conclude that angiogenesis-associated genes are regulated in a different manner in the two subgroups, and that the gene expression profiles of early- and late-onset PE diverge, supporting the hypothesis of early- and late-onset PE being at least partly two separate entities.
机译:产前先兆子痫(PE)背后的潜在机制仍不清楚。 PE的表现是异质性的,因此有人提出它是一种具有不同原因的综合征,而不是一种具有特定病因的疾病。最近,我们显示了两个亚组-早发和晚发PE之间循环血管生成因子的差异。为了进一步阐明两者之间的差异,我们研究了胎盘基因表达谱。全基因组微阵列技术和生物信息学分析被用于评估早期(24-32个孕周,n = 8)和迟发(36-41个孕周,n = 7)PE在胎盘中的基因表达谱。使用定量实时(qRT)–PCR验证了结果。我们发现早发性PE与早发性PE相比,196个基因的表达存在显着差异,这些基因中的45个显示2倍以上的倍数变化。生物信息学分析表明,血管生成和细胞运动的调节发生了变化。两种与血管新生相关的转录本(Egf17和Acvrl1)在早发性PE中的表达低于晚发性PE(P = 0.037和P = 0.003),在胎龄匹配的对照中也较低(P = 0.007和P = 0.011)。我们得出结论,在两个亚组中,与血管生成相关的基因受到不同方式的调控,而且早发和晚发性PE的基因表达谱存在差异,支持早发和晚发PE的假设至少部分是两个单独的实体。

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