Molecular Mechanisms of Trophoblast Dysfunction Mediated by Imbalance between STOX1 Isoforms
2020
Ducat, Aurélien | Couderc, Betty | Bouter, Anthony | Biquard, Louise | Aouache, Rajaa | Passet, Bruno | Doridot, Ludivine | Cohen, Marie-Benoîte | Ribaux, Pascale | Apicella, Clara | Palfray, Sophia | Chen, Yulian | Vargas, Alexandra | Julé, Amélie | Frelin, Léo | Cocquet, Julie | Ruano San Martin, Camino | Jacques, Sébastien | Busato, Florence | Tost, Jorg | Mehats, Céline | Laissue, Paul | Vilotte, Jean-Luc | Miralles, Francisco | Vaiman, Daniel | Institut Cochin (IC UM3 (UMR 8104 / U1016)) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité) | Chimie et Biologie des Membranes et des Nanoobjets (CBMN) ; Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS) | Génétique Animale et Biologie Intégrative (GABI) ; AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Université de Genève = University of Geneva (UNIGE) | Institut de Biologie François JACOB (JACOB) ; 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)
International audience
اظهر المزيد [+] اقل [-]إنجليزي. <div><p>STOX1 is a transcription factor involved in preeclampsia and Alzheimer disease. We show that the knock-down of the gene induces rather mild effect on gene expression in trophoblast cell lines (BeWo). We identified binding sites of STOX1 shared by the two major isoforms, STOX1A and STOX1B. Profiling gene expression of cells overexpressing either STOX1A or STOX1B, we identified genes downregulated by both isoforms, with a STOX1 binding site in their promoters. Among those, STOX1-induced Annexin A1 downregulation led to abolished membrane repair in BeWo cells. By contrast, overexpression of STOX1A or B has opposite effects on trophoblast fusion (acceleration and inhibition, respectively) accompanied by syncytin genes deregulation. Also, STOX1A overexpression led to abnormal regulation of oxidative and nitrosative stress. In sum, our work shows that STOX1 isoform imbalance is a cause of gene expression deregulation in the trophoblast, possibly leading to placental dysfunction and preeclampsia.</p></div>
اظهر المزيد [+] اقل [-]المعلومات البيبليوغرافية
تم تزويد هذا السجل من قبل Institut national de la recherche agronomique