Expression of markers of endoplasmic reticulum stress-induced apoptosis in the placenta of women with early and late onset severe pre-eclampsia
Expression of markers of endoplasmic reticulum stress-induced apoptosis in the placenta of women with early and late onset severe pre-eclampsia
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DOI：
10.1016/j.tjog.2014.11.002
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发表时间：
2015-02-01
影响因子：
2.1
通讯作者：
Zhu, Xiaohe
中科院分区：
文献类型：
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作者：
Fu, Jinhua;Zhao, Long;Zhu, Xiaohe
目的：内质网(ER)应激诱导的细胞凋亡与重度子痫前期(SPE)有关，其特点是激活了三条信号通路：PKR样内质网激酶(PERK)、激活转录因子6(ATF6)和肌醇需求1(IRE1)。本研究旨在探讨内质网应激在SPE发病机制中的作用。材料和方法：采集32例正常妊娠妇女的胎盘组织和两组早发和晚发SPE患者的胎盘组织。结果：胎盘组织中葡萄糖调节蛋白78(GRP78)、PERK、真核细胞起始因子2亚单位α(eIF2α)、激活转录因子6(ATF4)、ATF6、IRE1、CHOP(CIEBP同源蛋白)和caspase12mRNA及蛋白的表达水平明显高于正常对照组(P<0.05)。结论：内质网应激诱导的细胞凋亡在SPE的发生发展中起重要作用，尤其是在早发性SPE中，其机制可能与PERK信号通路的激活有关。版权所有(C)2014，台湾妇产科协会。爱思唯尔台湾有限责任公司出版。版权所有。
Objectives: Endoplasmic reticulum (ER) stress-induced apoptosis has been implicated in severe pre-eclampsia (SPE) and is characterized by the activation of three signaling pathways: PKR-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring 1 (Ire1). This study was designed to investigate the role of ER stress in the pathogenesis of SPE.Materials and methods: Placental tissues were collected from 32 women with normal pregnancies and two cohorts of women with early (n = 32) or late onset (n = 32) SPE. The expression of glucose-regulated protein 78 (GRP78), PERK, eukaryotic initiation factor 2 subunit a (eIF2 alpha), activating transcription factor 6 (ATF4), ATF6, Ire1, CHOP (CIEBP homologus protein), and caspase 12 mRNA and protein in the placentas was analyzed using real-time reverse transcription-polymerase chain reaction and Western blotting, respectively.Results: The levels of GRP78, PERK, eIF2 alpha, CHOP, ATF6, and caspase 12 mRNA and protein expression were significantly higher in the placentas of women with early and late SPE than in the control women, whereas there were no differences in ATF6 and Ire1 mRNA and protein.Conclusion: ER stress-induced apoptosis was important in the development of SPE, especially in early onset SPE and was probably due to the activation of the PERK signaling pathway. Copyright (C) 2014, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. All rights reserved.