1. Soluble CD146 is increased in preeclampsia and interacts with galectin-1 to regulate trophoblast migration through VEGFR2 receptor
- Author
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Ahmad Joshkon, Alexandrine Foucault-Bertaud, Wael Traboulsi, Christophe Demattei, Françoise Dignat-George, Nadia Alfaidy, Richard Bachelier, Odile Paulmyer-Lacroix, Jean-Christophe Gris, Aurélie S. Leroyer, Marcel Blot-Chabaud, Sylvie Bouvier Pharm, V. Letouzey, Nathalie Bardin, Mathieu Fortier, Sandra M. Blois, Marie Nollet, Eve Mousty, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Laboratoire de Biostatistique, Epidémiologie clinique, Santé Publique Innovation et Méthodologie [CHU Nîmes] (BESPIM), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Mécanisme de l’Angiogenèseet des BarrièresBiologiques (MAB2), BioSanté (UMR BioSanté), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Sechenov First Moscow State Medical University, Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Université de Montpellier (UM), Institut de Recherches en Technologies et Sciences pour le Vivant (IRTSV), and GRIS, Jean-Christophe
- Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology ,Galectin 1 ,MESH: Pre-Eclampsia ,MESH: Trophoblasts ,CD146 Antigen ,[SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics ,Preeclampsia ,Andrology ,MESH: Pregnancy ,Pre-Eclampsia ,Trophoblast migration ,Pregnancy ,Galectin-1 ,Blocking antibody ,Soluble CD146 could be proposed as a biomarker in preeclampsia and a potential therapeutic target ,medicine ,Humans ,Prospective Studies ,Receptor ,reproductive and urinary physiology ,MESH: Galectin 1 ,MESH: Humans ,Eclampsia ,business.industry ,Trophoblast ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,medicine.disease ,Trophoblasts ,MESH: Prospective Stufies ,carbohydrates (lipids) ,[SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics ,medicine.anatomical_structure ,CD146/sCD146 ,Female ,Signal transduction ,MESH: CD146 Antigen ,business ,MESH: Female - Abstract
International audience; Objective: To explore the regulatory role of soluble CD146 (sCD146) and its interaction with galectin-1 (Gal1) in placenta-mediated complications of pregnancy.Design: Prospective pilot and experimental studies.Setting: University-affiliated hospital and academic research laboratory.Patient(s): One hundred fifteen women divided into three groups: 30 healthy, nonpregnant women, 50 women with normal pregnancies, and 35 with placenta-mediated pregnancy complications.Intervention(s): Wound-healing experiments were conducted to study trophoblast migration.Main outcome measure(s): Quantification of sCD146 and Gal1 by enzyme-linked immunosorbent assay. Analysis of trophoblast migration by wound closure.Result(s): Concomitant detection of sCD146 and Gal1 showed lower sCD146 and higher Gal1 concentrations in women with normal pregnancies compared with nonpregnant women. In addition, follow-up of these women revealed a decrease in sCD146 associated with an increase in Gal1 throughout pregnancy. In contrast, in women with preeclampsia, we found significantly higher sCD146 concentrations compared with women with normal pregnancies and no modification of Gal1. We emphasize the opposing effects of sCD146 and Gal, since, unlike Gal1, sCD146 inhibits trophoblast migration. Moreover, the migratory effect of Gal1 was abrogated with the use of an anti-CD146 blocking antibody or the use of small interfering RNA to silence VEGFR2 expression. This suggests that trophoblast migration is mediated though the interaction of Gal1 with CD146, further activating the VEGFR2 signaling pathway. Significantly, sCD146 blocked the migratory effects of Gal1 on trophoblasts and inhibited its secretion, suggesting that sCD146 acts as a ligand trap.Conclusion(s): Soluble CD146 could be proposed as a biomarker in preeclampsia and a potential therapeutic target. Clinical trial registration number: NCT 01736826.Trial registration: ClinicalTrials.gov NCT01736826.
- Published
- 2022