title: Up-regulated expression and aberrant DNA methylation of LEP and SH3PXD2A in pre-eclampsia.
abstract: 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.
authors.affiliation: Children's Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Xiang
authors.forename: Yan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Li
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Li
authors.forename: Jiawei
authors.initials: J
authors.lastname: Xu
authors.forename: Junyu
authors.initials: J
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Qinghe
authors.initials: Q
authors.lastname: Xing
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.forename: Xinzhi
authors.initials: X
authors.lastname: Zhao
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D016022:Case-Control Studies; D002460:Cell Line; D019295:Computational Biology; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D020738:Leptin / Q000235:genetics* / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D020738:Leptin; D012333:RNA, Messenger; C478582:SH3PXD2A protein, human; D008156:Luciferases
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