Sun Cheng-Juan, Zhang Wei-Yuan, Yu Song, Cui Man-Hua
Department of Obstetrics, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.
Zhonghua Fu Chan Ke Za Zhi. 2008 Sep;43(9):651-6.
To investigate genes involved in the mechanisms underlying the progression of severe preeclampsia.
We conducted a multiregional gene expression analysis using peripheral leucocytes from patients with preeclampsia and normal controls. Total RNA was extracted from peripheral blood of six severe preeclampsia and five normotensive pregnancies. We performed genome-wide expression profiling using Affymetrix HG_U133 plus 2.0 chips to screen out differentially expressed genes of 2 fold or more and q_value < 5.4%. Using Gene Ontology we identified the function of differentially expressed genes after cluster analysis.
Among the 47 000 genes that were screened in the microarray, 140 genes were found to be differentially expressed between normal and preeclamptic pregnancies. Eighty six up-regulated candidate genes were mainly involved in cysteine metabolism urea cycle and metabolism of amiogroups, proteasome, TGF-beta signaling pathway, and the ratio of calponin2 (CNN2), matrix metallopeptidase 8 (MMP8), V-set and immunoglobulin domain containing 4 (VSIG4), proteasome 26S subunit ATPase 5 (PSMC5) was evidently increased in preeclampsia patients. Among 54 down-regulated candidates, natural killer cell mediated cytotoxicity, antigen processing and presentation, metabolism of xenobiotics by cytochrome P450 were the main pathways. KIR3DL2, AKR1C3, CHURC1 and SLC25A13 were obviously decreased in preeclampsia patients.
The gene expression of peripheral leucocytes in preeclampsia patients is significantly different from that of uncomplicated pregnancies. CNN2, MMP8, VSIG4, PSMC5, KIR3DL2, AKR1C3, CHURC1 and SLC25A13 may be involved in the molecular mechanisms underlying the progression of severe preeclampsia.
研究与重度子痫前期进展机制相关的基因。
我们使用子痫前期患者和正常对照者的外周血白细胞进行了多区域基因表达分析。从6例重度子痫前期患者和5例血压正常孕妇的外周血中提取总RNA。我们使用Affymetrix HG_U133 plus 2.0芯片进行全基因组表达谱分析，以筛选出差异表达2倍或以上且q值<5.4%的基因。使用基因本体论在聚类分析后确定差异表达基因的功能。
在微阵列筛选的47000个基因中，发现140个基因在正常妊娠和子痫前期妊娠之间存在差异表达。86个上调的候选基因主要参与半胱氨酸代谢、尿素循环和氨基基团代谢、蛋白酶体、转化生长因子-β信号通路，并且在子痫前期患者中，钙调蛋白2（CNN2）、基质金属蛋白酶8（MMP8）、含V结构域和免疫球蛋白结构域4（VSIG4）、蛋白酶体26S亚基ATP酶5（PSMC5）的比例明显增加。在54个下调的候选基因中，自然杀伤细胞介导的细胞毒性、抗原加工和呈递、细胞色素P450对外源生物的代谢是主要途径。子痫前期患者中杀伤细胞免疫球蛋白样受体3DL2（KIR3DL2）、醛酮还原酶家族1成员C3（AKR1C3）、卷曲螺旋结构域蛋白1（CHURC1）和溶质载体家族25成员13（SLC25A13）明显减少。
子痫前期患者外周血白细胞的基因表达与正常妊娠有显著差异。CNN2、MMP8、VSIG4、PSMC5、KIR3DL2、AKR1C3、CHURC1和SLC25A13可能参与重度子痫前期进展的分子机制。
