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Preeclampsia associates with RECK-dependent decrease in human trophoblasts migration and invasion
Affiliation:1. Reproductive Medical Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, China;2. Departments of Gynecology and Obstetrics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China;3. Department of Obstetrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China;4. Department of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Nanning, China;1. Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile;2. Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen (UMCG), Groningen, 9700 RB, The Netherlands;3. Department of Basic Sciences, Faculty of Sciences, Universidad del Bío-Bío, Chillán 3780000, Chile;4. Gynaecology and Obstetrics Service, Hospital San Juan de Dios, Santiago 8330024, Chile;5. Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, Seville E-41012, Spain;6. Metabolic Diseases Research Laboratory, Center of Research, Development and Innovation in Health - Aconcagua Valley, San Felipe Campus, School of Medicine, Faculty of Medicine, Universidad de Valparaíso, San Felipe 2172972, Chile;7. University of Queensland, Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston, QLD 4029, Queensland, Australia
Abstract:IntroductionPreeclampsia is characterized by reduced invasion capacity of trophoblasts involving lower matrix metalloproteinase (MMP) activity. Cell invasion is reduced by reversion-inducing-cysteine-rich protein with Kazal motifs (RECK), a plasma membrane protein that inhibits MMP in several cell types. However, it is unknown whether this mechanism happens in the human placenta from preeclampsia. The hypothesis of this study sustains that RECK expression is increased leading to reduced trophoblasts invasion in preeclampsia.MethodsRECK expression in the human first trimester trophoblast cell line HTR8/SvNeo and in placentas from normal (n = 4) and preeclampsia (n = 4) pregnancies was evaluated by Western blot and immunofluorescence. MMP-dependent gelatin hydrolyzation was measured by in situ zymography and gelatinase assay in placental and cell extracts. RECK was overexpressed (plasmidial vector transfection) or partially reduced (shRNA) to evaluate its role in HTR8/SVneo cell migration and invasion.ResultsRECK was expressed in trophoblasts layer in human placentas. Preeclampsia resulted in higher placental RECK protein abundance, reduced MMP function, and higher level of fibronectin (a MMP substrate) compared with placentas from normal pregnancies. RECK is also expressed in HTR-8/SVneo cells. Reduced RECK expression resulted in higher MMP-dependent gelatin hydrolyzation, associated to higher migration and invasion of HTR8/SVneo cells. However, RECK overexpression associated with reduced hydrolyzation, cell migration and invasion.DiscussionRECK is overexpressed in human trophoblasts from preeclampsia and may be responsible of this disease-associated lower migration and invasion of this cell type.
Keywords:RECK  Human trophoblast  Migration  Invasion  Preeclampsia  Human placenta
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