PDF(Pubmed)
Abstract：
Preeclampsia (PE) is a pregnancy-specific disorder associated with shallow invasion of the trophoblast cells and insufficient remodeling of the uterine spiral artery. Protein glycosylation plays an important role in trophoblast cell invasion. However, the glycobiological mechanism of PE has not been fully elucidated. In the current study, employing the Lectin array, we found that soybean agglutinin (SBA), which recognizes the terminal N-acetylgalactosamine α1,3-galactose (GalNAc α1,3 Gal) glycotype, was significantly increased in placental trophoblast cells from PE patients compared with third-trimester pregnant controls. Upregulating the expression of the key enzyme α1,3 N-acetylgalactosaminyl transferase (GTA) promoted the biosynthesis of terminal GalNAc α1,3 Gal and inhibited the migration/invasion of HTR8/SVneo trophoblast cells. Moreover, the methylation status of GTA promoter in placental tissues from PE patients was lower than that in the third trimester by methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP) analysis. Elevated GTA expression in combination with the DNA methylation inhibitor 5-azacytidine (5-AzaC) treatment increased the glycotype biosynthesis and impaired the invasion potential of trophoblast cells, leading to preeclampsia. This study suggests that elevated terminal GalNAc α1,3 Gal biosynthesis and GTA expression may be applied as the new markers for evaluating placental function and the auxiliary diagnosis of preeclampsia.
摘要：
先兆子痫（PE）是一种妊娠特异性疾病，与滋养细胞的浅层侵入和子宫螺旋动脉的重塑不足有关。蛋白质糖基化在滋养细胞的侵袭中起着重要作用。然而,PE的糖生物学机制尚未完全阐明。在目前的研究中,使用凝集素阵列，我们发现大豆凝集素(SBA)，它识别末端N-乙酰半乳糖胺α1,3-半乳糖（GalNAcα1,3Gal）糖类型，与妊娠晚期对照组相比，PE患者的胎盘滋养层细胞显着增加。上调关键酶α1,3N-乙酰半乳糖胺基转移酶（GTA）的表达促进了末端GalNAcα1,3Gal的生物合成，并抑制了HTR8/SVneo滋养层细胞的迁移/侵袭。此外，通过甲基化特异性PCR（MSP）和亚硫酸氢盐测序PCR（BSP）分析，PE患者胎盘组织中GTA启动子的甲基化状态低于妊娠晚期。升高的GTA表达与DNA甲基化抑制剂5-氮杂胞苷（5-AzaC）处理相结合增加了糖类型生物合成并损害了滋养层细胞的侵袭潜力，导致先兆子痫.这项研究表明，晚期GalNAcα1,3Gal生物合成和GTA表达升高可作为评估胎盘功能和子痫前期辅助诊断的新标志物。
