Gestational age-related patterns of AMOT methylation are revealed in preterm infant endothelial progenitors
| Autor: | Florent Dumont, Farid Boubred, Thierry Fournier, G. Vinci, Christophe Buffat, Françoise Dignat-George, Stéphanie Simoncini, Isabelle Ligi, Daniel Vaiman, Bernard Le Bonniec, Umberto Simeoni |
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| Přispěvatelé: | Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Caen Normandie - UFR Santé (UNICAEN Santé), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Innovations thérapeutiques en hémostase (IThEM - U1140), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Angiogenesis Physiology lcsh:Medicine Blood Pressure Cardiovascular Physiology Biochemistry Vascular Medicine Epigenesis Genetic 0302 clinical medicine Medicine and Health Sciences Medicine lcsh:Science Promoter Regions Genetic [SDV.BDD]Life Sciences [q-bio]/Development Biology Endothelial Progenitor Cells Multidisciplinary DNA methylation Microfilament Proteins Gestational age Methylation Fetal Blood Chromatin Body Fluids Nucleic acids Blood CpG site 030220 oncology & carcinogenesis Cord blood Infant Small for Gestational Age Hypertension Intercellular Signaling Peptides and Proteins Female Epigenetics Anatomy DNA modification Infant Premature Chromatin modification Maternal Age Research Article Chromosome biology Adult Cell biology Real-Time Polymerase Chain Reaction Andrology 03 medical and health sciences Vasculogenesis [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] CpG Islands DNA Methylation Endothelial Progenitor Cells/metabolism Fetal Blood/metabolism Humans Infant Premature/growth & development Infant Premature/metabolism Infant Small for Gestational Age/growth & development Infant Small for Gestational Age/metabolism Intercellular Signaling Peptides and Proteins/genetics Intercellular Signaling Peptides and Proteins/metabolism Membrane Proteins/genetics Membrane Proteins/metabolism Sequence Analysis DNA Genetics Treatment Guidelines Health Care Policy Biology and life sciences business.industry lcsh:R Membrane Proteins Neonates DNA Health Care 030104 developmental biology Angiomotins lcsh:Q Gene expression business Developmental Biology |
| Zdroj: | PloS one, vol. 12, no. 10, pp. e0186321 PLoS ONE PLoS ONE, Public Library of Science, 2017, 12 (10), pp.e0186321. ⟨10.1371/journal.pone.0186321⟩ PLoS ONE, 2017, 12 (10), pp.e0186321. ⟨10.1371/journal.pone.0186321⟩ PLoS ONE, Vol 12, Iss 10, p e0186321 (2017) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0186321⟩ |
| Popis: | International audience; Objective: Preterm birth is associated with altered angiogenesis and with increased risk of cardiovascular dysfunction and hypertension at adulthood. We previously demonstrated that in preterm newborns circulating cord blood endothelial progenitor cells (ECFC), responsible for angio/vasculogenesis, are reduced in number and display altered angiogenic properties. Altered angiogenic function was associated with a decreased expression of pro-angiogenic genes, among which the AMOT gene which is a strong positive regulator of angiogenesis. Such dysregulation may be related to epigenetic factors. In this study we analyse the methylation profiling of the AMOT gene during development, through a comparative analysis of the cord blood ECFC of preterm newborns and their term counterpart.Methods: We used both cloning-sequencing and pyrosequencing experiments to perform a comparative analysis of the DNA methylation profile of the promoter CpG island of AMOT gene in the cord blood ECFC of 16 preterm newborns (28–35 weeks gestational age-GA) and 15 term newborns (>37 weeks GA).Results: Twenty nine clones (obtained from 2 term newborns) and forty clones (obtained from 3 preterm newborns) were sequenced. The AMOT gene methylation rate was significantly higher in preterm compared to term newborns (4.5% versus 2.5% respectively: χ2 = 3.84; P = 1.8 10−02). Bisulfite pyrosequencing identified four CpG dinucleotides with significantly higher methylation levels in preterm newborns. This CpG-targeted methylation significantly decreased with increasing gestational age.Conclusions: These findings highlight importance of pro-angiogenic AMOT gene methylation in ECFC, suggesting that epigenetic mechanisms may control the regulation of angiogenesis during development. Therefore they pave the way to specific short term and long term complications of preterm birth by altered angiogenesis. |
| Databáze: | OpenAIRE |
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