Up-regulated expression and aberrant DNA methylation of LEP and SH3PXD2A in pre-eclampsia.
Up-regulated expression and aberrant DNA methylation of LEP and SH3PXD2A in pre-eclampsia.
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先兆子痫中 LEP 和 SH3PXD2A 的上调表达和异常 DNA 甲基化
DOI：
10.1371/journal.pone.0059753
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zhao X
中科院分区：
文献类型：
--
作者：
Xiang Y;Cheng Y;Li X;Li Q;Xu J;Zhang J;Liu Y;Xing Q;Wang L;He L;Zhao X
先兆子痫（PE）的主要机制仍然是妇产科最紧迫的问题之一。在本研究中，我们进行了表达谱筛选，检测到 PE 胎盘中差异表达（p<0.05 且倍数变化 >1.5）的 1312 个基因，包括 LEP 和 SH3PXD2A。验证微阵列结果后，我们对先兆子痫 (n = 16) 与正常胎盘 (n = 16) 中的 LEP 和 SH3PXD2A 进行了定量甲基化分析。结果表明，与对照组相比，PE妊娠胎盘中靠近LEP基因转录起始位点（TSS）的许多CpG位点低甲基化，包括TSS位置（p = 0.001）、Sp1（p = 1.57×10−4）、LP1（p = 0.023）和CEBPα的结合位点(p = 0.031)。荧光素酶报告基因分析证实LEP启动子的异常甲基化和CEBPα共转染在基因表达调控中发挥作用。我们的结果表明异常的 LEP 启动子甲基化参与了 PE 的发展。我们没有发现SH3PXD2A启动子区域的组间显着甲基化差异，然而，基因体中的CGI区域（CGI34）在先兆子痫胎盘中表现出较高的甲基化（p = 1.57×10−4），这可能会促进基因转录的效率。我们推测SH3PXD2A可能通过其在胎盘形成期调节滋养层细胞侵袭的作用参与了PE的发病机制。
The primary mechanism underlying pre-eclampsia (PE) remains one of the most burning problems in the obstetrics and gynecology. In this study, we performed an expression profiling screen and detected 1312 genes that were differentially expressed (p<0.05 and fold change >1.5) in PE placentas, including LEP and SH3PXD2A. After validating the microarray results, we conducted the quantitative methylation analysis of LEP and SH3PXD2A in preeclamptic (n = 16) versus normal placentas (n = 16). Our results showed that many CpG sites close to the transcriptional start site (TSS) of LEP gene were hypomethylated in placentas from pregnancies with PE compared with those of in controls, including the TSS position (p = 0.001), the binding sites of Sp1 (p = 1.57×10−4), LP1 (p = 0.023) and CEBPα (p = 0.031). Luciferase reporter analysis confirmed the aberrant methylation of LEP promoter and CEBPα co-transfection had a role in the regulation of gene expression. Our results indicated the aberrant LEP promoter methylation was involved in the development of PE. We did not find a significant methylation differences between groups in the promoter region of SH3PXD2A, however, a CGI region in the gene body (CGI34) presented a higher methylation in preeclamptic placentas (p = 1.57×10−4), which might promote the efficiency of gene transcription. We speculated that SH3PXD2A may take part in the pathogenesis of PE through its role in the regulation of trophoblast cell invasion in the period of placenta formation.
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影响因子：
3.2
作者：
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