title: Leukemia inhibitory factor promote trophoblast invasion via urokinase-type plasminogen activator receptor in preeclampsia.
abstract: Preeclampsia is a pregnancy-related syndrome which can cause perinatal mortality and morbidity. Inadequate invasion by trophoblast cells may lead to poor perfusion of the placenta, even result in preeclampsia. Understanding the molecular mechanisms underlying placentation facilitates the better intervention of preeclampsia. Urokinase-type plasminogen activator receptor (uPAR) is involved in the physiological and pathological processes. Leukemia inhibitory factor (LIF) is an important regulator in the establishment of pregnancy. However, the expression of uPAR in preeclamptic patients and its relationship with LIF remains unclear. In the current study, we found that the level of uPAR was relatively lower in the placentas from preeclamptic patients as compared with normal pregnant women. LIF promoted trophoblast cell outgrowth by upregulating uPAR in an explants culture, and LIF also enhanced migration and invasion potential through uPAR in trophoblast JAR and JEG-3 cell lines, and with increased gelatinolytic activities of matrix metalloproteinase 2 (MMP-2). The effect of LIF and uPAR on trophoblast migration and invasion was mediated by PI3K/AKT signaling pathway. Our data indicates the roles of LIF in promoting trophoblast migration and invasion through uPAR and suggest that abnormal expression of uPAR might be associated with the etiology of preeclampsia.
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian 116044, People's Republic of China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian 116044, People's Republic of China.
authors.forename: Kuixing
authors.initials: K
authors.lastname: Dai
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian 116044, People's Republic of China.
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian 116044, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian 116044, People's Republic of China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, The first Affiliated Hospital of Dalian Medical University, Dalian 116000, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yan
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian 116044, People's Republic of China. Electronic address: liushuai_129@163.com.
authors.forename: Shuai
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian 116044, People's Republic of China. Electronic address: yanqiu63@126.com.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Yan
mesh_terms: D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology*; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D053605:Leukemia Inhibitory Factor; D055293:Receptors, Urokinase Plasminogen Activator; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Invasion; LIF; PI3K/Akt; Preeclampsia; Trophoblast; uPAR