title: Preeclamptic plasma induces transcription modifications involving the AP-1 transcriptional regulator JDP2 in endothelial cells.
abstract: Preeclampsia is a pregnancy disorder characterized by hypertension and proteinuria. In preeclampsia, the placenta releases factors into the maternal circulation that cause a systemic endothelial dysfunction. Herein, we investigated the effects of plasma from women with preeclamptic and normal pregnancies on the transcriptome of an immortalized human umbilical vein endothelial cell line. The cells were exposed for 24 hours to preeclamptic or normal pregnancy plasma and their transcriptome was analyzed using Agilent microarrays. A total of 116 genes were found differentially expressed: 71 were up-regulated and 45 were down-regulated. In silico analysis revealed significant consistency and identified four functional categories of genes: mitosis and cell cycle progression, anti-apoptotic, fatty acid biosynthesis, and endoplasmic reticulum stress effectors. Moreover, several genes involved in vasoregulation and endothelial homeostasis showed modified expression, including EDN1, APLN, NOX4, and CBS. Promoter analysis detected, among the up-regulated genes, a significant overrepresentation of genes containing activation protein-1 regulatory sites. This correlated with down-regulation of JDP2, a gene encoding a repressor of activation protein-1. The role of JDP2 in the regulation of a subset of genes in the human umbilical vein endothelial cells was confirmed by siRNA inhibition. We characterized transcriptional changes induced by preeclamptic plasma on human umbilical vein endothelial cells, and identified, for the first time to our knowledge, JDP2 as a regulator of a subset of genes modified by preeclamptic plasma.
authors.affiliation: Institut National de la Sante et la Recherche Medicale U1016-Centre National de la Recherche Scientifique UMR8104, Université Paris Descartes, Institut Cochin, Paris, France.
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Calicchio
authors.affiliation: Molecular Biology Laboratory, Genetics and Endocrine Oncology, Hôpital de la Conception-Assistance Publique-Hopitaux de Marseille, Marseille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Buffat
authors.affiliation: Institut National de la Sante et la Recherche Medicale U1016-Centre National de la Recherche Scientifique UMR8104, Université Paris Descartes, Institut Cochin, Paris, France.
authors.forename: Jacques R
authors.initials: JR
authors.lastname: Mathieu
authors.affiliation: Institut National de la Sante et la Recherche Medicale U1016-Centre National de la Recherche Scientifique UMR8104, Université Paris Descartes, Institut Cochin, Paris, France; Biochemistry Laboratory, Centre Hospitalier Universitaire Farhat Hached, Sousse, Tunisia.
authors.forename: Nour
authors.initials: N
authors.lastname: Ben Salem
authors.affiliation: Institut National de la Sante et la Recherche Medicale U1016-Centre National de la Recherche Scientifique UMR8104, Université Paris Descartes, Institut Cochin, Paris, France.
authors.forename: Celine
authors.initials: C
authors.lastname: Mehats
authors.affiliation: Institut National de la Sante et la Recherche Medicale U1016-Centre National de la Recherche Scientifique UMR8104, Université Paris Descartes, Institut Cochin, Paris, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Jacques
authors.affiliation: Department of Obstetrics and Gynecology, Reproductive Medicine, Hôpital Tenon, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Hertig
authors.affiliation: Department of Obstetrics and Gynecology, Reproductive Medicine, Hôpital Tenon, Paris, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Berkane
authors.affiliation: Gynecology and Obstetrics Service, AP-HP Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Grevoul-Fresquet
authors.affiliation: Molecular Biology Laboratory, Genetics and Endocrine Oncology, Hôpital de la Conception-Assistance Publique-Hopitaux de Marseille, Marseille, France.
authors.forename: Umberto
authors.initials: U
authors.lastname: Simeoni
authors.affiliation: Institut National de la Sante et la Recherche Medicale U1016-Centre National de la Recherche Scientifique UMR8104, Université Paris Descartes, Institut Cochin, Paris, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Peyssonnaux
authors.affiliation: Institut National de la Sante et la Recherche Medicale U1016-Centre National de la Recherche Scientifique UMR8104, Université Paris Descartes, Institut Cochin, Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Gavard
authors.affiliation: Institut National de la Sante et la Recherche Medicale U1016-Centre National de la Recherche Scientifique UMR8104, Université Paris Descartes, Institut Cochin, Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Vaiman
authors.affiliation: Institut National de la Sante et la Recherche Medicale U1016-Centre National de la Recherche Scientifique UMR8104, Université Paris Descartes, Institut Cochin, Paris, France. Electronic address: francisco.miralles@inserm.fr.
authors.forename: Francisco
authors.initials: F
authors.lastname: Miralles
mesh_terms: D000328:Adult; D002461:Cell Line, Transformed; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D010949:Plasma / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000097:blood / Q000473:pathology; D011247:Pregnancy; D012097:Repressor Proteins / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D059467:Transcriptome
chemical_list: C491387:JDP2 protein, human; D012097:Repressor Proteins; D018808:Transcription Factor AP-1