SRC-3 Plays a Critical Role in Human Umbilical Vein Endothelial Cells by Regulating the PI3K/Akt/mTOR Pathway in Preeclampsia
SRC-3 Plays a Critical Role in Human Umbilical Vein Endothelial Cells by Regulating the PI3K/Akt/mTOR Pathway in Preeclampsia
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SRC-3 通过调节先兆子痫中的 PI3K/Akt/mTOR 通路在人脐静脉内皮细胞中发挥关键作用
DOI：
10.1177/1933719117725818
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发表时间：
2018
影响因子：
2.9
通讯作者：
Qi Hongbo
中科院分区：
文献类型：
--
作者：
Yuan Yu;Shan Nan;Tan Bin;Deng Qinyin;Liu Yangming;Wang Hanbin;Luo Xiaofang;He Chengjin;Luo Xin;Zhang Hua;Baker Philip N;Olson David M;Qi Hongbo
子痫前期(PE)目前被认为是以氧化应激为特征的，氧化应激可能导致内皮功能障碍。血管内皮细胞的正常功能是维持血管内环境稳定的关键。以往的研究表明，类固醇受体共激活因子3(SRC-3)与雌激素受体(ER)相互作用，雌激素受体参与雌激素的血管保护作用，并与细胞迁移、侵袭和炎症有关，但其在PE中的作用尚不清楚。本研究的主要目的是探讨SRC-3在人脐静脉内皮细胞(HUVECs)发生、发展过程中的作用。我们的研究表明，SRC-3在PE胎盘中的表达明显低于正常胎盘。此外，针对SRC-3的慢病毒短发夹状RNA和缺氧/复氧处理可减弱HUVEC的迁移和管状形成能力，并促进HUVEC的凋亡。此外，我们在PI3K/Akt/哺乳动物靶点雷帕霉素(MTOR)信号通路中检测到可能的下游活性，这与SRC-3介导的HUVEC功能有关。我们的数据表明，氧化应激在调控SRC-3表达中起着关键作用，SRC-3通过PI3K/Akt/mTor信号通路影响内皮细胞的迁移和管状形成能力。这一作用可能导致PE的发病机制。
Preeclampsia (PE) is currently thought to be characterized by oxidative stress which may lead to endothelial dysfunction. The normal function of vascular endothelium is essential to vascular homeostasis. Previous studies have shown that steroid receptor coactivator 3 (SRC-3) interacts with estrogen receptors (ERs) which are involved in the vasoprotective effects of estrogen and is also associated with cell migration, invasion, and inflammation; however, its role in PE remains unclear. The main purpose of this study is to identify the role of SRC-3 in the function of human umbilical vein endothelial cells (HUVECs) during the development of PE. Our study demonstrated that the expression of SRC-3 was significantly decreased in PE placentas compared to normal placentas. Additionally, lentivirus short hairpin RNA against SRC-3 and hypoxia/reoxygenation treatments attenuated migration and tube formation abilities and enhanced HUVEC apoptosis. Furthermore, we detected possible downstream in the PI3K/Akt/mammalian target of rapamycin (mTOR) signal pathway activity, which is involved in SRC-3-mediated HUVEC function. Our data suggest that oxidative stress plays a crucial role in controlling SRC-3 expression, which influences the migration and tube formation abilities of endothelial cells through the PI3K/Akt/mTOR signaling pathways. This action may then result in PE pathogenesis.