title: Regulation of Human Trophoblast GLUT3 Glucose Transporter by Mammalian Target of Rapamycin Signaling.
abstract: Glucose transporter isoform-3 (GLUT3), one of the primary placental facilitative glucose transporters responsible for basal glucose transport, has a crucial role in glucose transport and fetal growth during early pregnancy. A GLUT3 mutation in mice has been reported to cause loss of early pregnancy or late-gestational fetal growth restriction. However, the underlying mechanisms that regulate the placental GLUT3 transporter in humans are largely unknown. In the present study, we used the JEG-3 human choriocarcinoma cell line, which resembles a first trimester placental model, to study the role of the mammalian target of rapamycin complex 1 (mTORC1) in the regulation of placental GLUT3. We combined rapamycin treatment and small interfering (si) RNA-mediated silencing approaches with mRNA and protein expression/localization studies to investigate the alteration of GLUT3 expression and localization following mTORC1 inhibition in JEG-3 trophoblasts. Inhibition of mTORC1 signaling by silencing raptor decreased GLUT3 mRNA expression (-41%) and protein expression (-50%). Similar effects were obtained in cells in which mTORC1 was inhibited by rapamycin. Immunofluorescence analysis revealed that GLUT3 expression was markedly reduced in the cell surface and cytoplasm of JEG-3 cells in response to mTORC1 silencing. Because placental mTORC1 activity and GLUT3 expression are decreased in human intrauterine growth restriction, our data suggested one possible mechanism for the abnormal fetal growth in this pregnancy complication.
authors.affiliation: Laboratory of Reproductive Endocrinology, Department of Physiology, Harbin Medical University, Harbin 150081, China. xujie@ems.hrbmu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Laboratory of Reproductive Endocrinology, Department of Physiology, Harbin Medical University, Harbin 150081, China. angel200202003@163.com.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Lu
authors.affiliation: Laboratory of Reproductive Endocrinology, Department of Physiology, Harbin Medical University, Harbin 150081, China. wangj_84321@163.com.
authors.forename: Jiao
authors.initials: J
authors.lastname: Wang
authors.affiliation: Laboratory of Reproductive Endocrinology, Department of Physiology, Harbin Medical University, Harbin 150081, China. qilinyehappy@163.com.
authors.forename: Ruotong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Laboratory of Reproductive Endocrinology, Department of Physiology, Harbin Medical University, Harbin 150081, China. qianxiaoniude@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Qian
authors.affiliation: Laboratory of Reproductive Endocrinology, Department of Physiology, Harbin Medical University, Harbin 150081, China. zhuhui@ems.hrbmu.edu.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhu
mesh_terms: D045744:Cell Line, Tumor; D051274:Glucose Transporter Type 3 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*
chemical_list: D051274:Glucose Transporter Type 3; D046912:Multiprotein Complexes; D012333:RNA, Messenger; C495687:SLC2A3 protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: glucose transporter isofrom-3; mammalian target of rapamycin; placenta