Liang Mengmeng, Niu Jianmin, Zhang Liang, Deng Hua, Ma Jian, Zhou Weiping, Duan Dongmei, Zhou Yuheng, Xu Huikun, Chen Longding
Department of Obstetrics, Guangdong Women and Children's Hospital, Guangzhou, 511400, China.
Department of Obstetrics, Guangdong Women and Children's Hospital, Guangzhou, 511400, China.
Placenta. 2016 Apr;40:52-9. doi: 10.1016/j.placenta.2016.02.015. Epub 2016 Feb 24.
Early-onset preeclampsia and late-onset preeclampsia have been regarded as two different phenotypes with heterogeneous manifestations; To gain insights into the pathogenesis of the two traits, we analyzed the gene expression profiles in preeclamptic placentas. A whole genome-wide microarray was used to determine the gene expression profiles in placental tissues from patients with early-onset (n = 7; <34 weeks), and late-onset (n = 8; >36 weeks) preeclampsia and their controls who delivered preterm (n = 5; <34 weeks) or at term (n = 5; >36 weeks). Genes were termed differentially expressed if they showed a fold-change ≥ 2 and q-value < 0.05. Quantitative real-time reverse transcriptase PCR was used to verify the results. Western blotting was performed to verify the expressions of secreted genes at the protein level.
Six hundred twenty-seven genes were differentially expressed in early-compared with late-onset preeclampsia (177 genes were up-regulated and 450 were down-regulated). Gene ontology analysis identified significant alterations in several biological processes; the top two were immune response and cell surface receptor linked signal transduction. Among the cell surface receptor linked signal transduction-related, differentially expressed genes, those involved in the G-protein coupled receptor protein signaling pathway were significantly enriched. G-protein coupled receptor signaling pathway related genes, such as GPR124 and MRGPRF, were both found to be down-regulated in early-onset preeclampsia. The results were consistent with those of western blotting that the abundance of GPR124 was lower in early-onset compared with late-onset preeclampsia. The different gene expression profiles reflect the different levels of transcription regulation between the two conditions and supported the hypothesis that they are separate disease entities. Moreover, the G-protein coupled receptor signaling pathway related genes may contribute to the mechanism underlying early- and late-onset preeclampsia.
早发型子痫前期和晚发型子痫前期被视为具有不同表现的两种不同表型；为深入了解这两种特征的发病机制，我们分析了子痫前期胎盘的基因表达谱。使用全基因组微阵列来确定早发型（n = 7；<34周）和晚发型（n = 8；>36周）子痫前期患者及其早产（n = 5；<34周）或足月分娩（n = 5；>36周）的对照者胎盘组织中的基因表达谱。如果基因的变化倍数≥2且q值<0.05，则将其称为差异表达基因。采用定量实时逆转录聚合酶链反应来验证结果。进行蛋白质印迹法以在蛋白质水平验证分泌基因的表达。
与晚发型子痫前期相比，早发型子痫前期中有627个基因差异表达（177个基因上调，450个基因下调）。基因本体分析确定了几个生物学过程中的显著变化；前两位是免疫反应和细胞表面受体相关信号转导。在细胞表面受体相关信号转导相关的差异表达基因中，参与G蛋白偶联受体蛋白信号通路的基因显著富集。发现G蛋白偶联受体信号通路相关基因，如GPR124和MRGPRF，在早发型子痫前期中均下调。结果与蛋白质印迹法一致，即早发型子痫前期中GPR124的丰度低于晚发型子痫前期。不同的基因表达谱反映了两种情况之间转录调控的不同水平，并支持它们是独立疾病实体的假设。此外，G蛋白偶联受体信号通路相关基因可能有助于早发型和晚发型子痫前期的潜在机制。
