PMID- 28826365 OWN - NLM STAT- MEDLINE DCOM- 20181107 LR - 20211204 IS - 1933-7205 (Electronic) IS - 1933-7191 (Linking) VI - 25 IP - 5 DP - 2018 May TI - SRC-3 Plays a Critical Role in Human Umbilical Vein Endothelial Cells by Regulating the PI3K/Akt/mTOR Pathway in Preeclampsia. PG - 748-758 LID - 10.1177/1933719117725818 [doi] AB - 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. FAU - Yuan, Yu AU - Yuan Y AD - 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. AD - 2 China-Canada-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China. FAU - Shan, Nan AU - Shan N AD - 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. AD - 2 China-Canada-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China. FAU - Tan, Bin AU - Tan B AD - 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. AD - 2 China-Canada-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China. FAU - Deng, Qinyin AU - Deng Q AD - 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. AD - 2 China-Canada-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China. FAU - Liu, Yangming AU - Liu Y AD - 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. AD - 2 China-Canada-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China. FAU - Wang, Hanbin AU - Wang H AD - 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. AD - 2 China-Canada-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China. FAU - Luo, Xiaofang AU - Luo X AD - 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. AD - 2 China-Canada-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China. FAU - He, Chengjin AU - He C AD - 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. AD - 2 China-Canada-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China. FAU - Luo, Xin AU - Luo X AD - 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. AD - 2 China-Canada-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China. FAU - Zhang, Hua AU - Zhang H AD - 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. AD - 2 China-Canada-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China. FAU - Baker, Philip N AU - Baker PN AD - 2 China-Canada-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China. FAU - Olson, David M AU - Olson DM AD - 2 China-Canada-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China. FAU - Qi, Hongbo AU - Qi H AUID- ORCID: 0000-0002-8463-3774 AD - 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. AD - 2 China-Canada-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170822 PL - United States TA - Reprod Sci JT - Reproductive sciences (Thousand Oaks, Calif.) JID - 101291249 RN - EC 2.3.1.48 (NCOA3 protein, human) RN - EC 2.3.1.48 (Nuclear Receptor Coactivator 3) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Adult MH - Female MH - Human Umbilical Vein Endothelial Cells/*metabolism MH - Humans MH - Nuclear Receptor Coactivator 3/*metabolism MH - Oxidative Stress MH - Phosphatidylinositol 3-Kinase/*metabolism MH - Placenta/metabolism MH - Pre-Eclampsia/*metabolism MH - Pregnancy MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Signal Transduction MH - TOR Serine-Threonine Kinases/*metabolism OTO - NOTNLM OT - PI3K/Akt/mTOR signaling pathway OT - SRC-3 OT - human umbilical vein endothelial cells OT - preeclampsia EDAT- 2017/08/23 06:00 MHDA- 2018/11/08 06:00 CRDT- 2017/08/23 06:00 PHST- 2017/08/23 06:00 [pubmed] PHST- 2018/11/08 06:00 [medline] PHST- 2017/08/23 06:00 [entrez] AID - 10.1177/1933719117725818 [doi] PST - ppublish SO - Reprod Sci. 2018 May;25(5):748-758. doi: 10.1177/1933719117725818. Epub 2017 Aug 22.