Biogenesis of Pro-senescent Microparticles by Endothelial Colony Forming Cells from Premature Neonates is driven by SIRT1-Dependent Epigenetic Regulation of MKK6.

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_8FFCA28035C9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Biogenesis of Pro-senescent Microparticles by Endothelial Colony Forming Cells from Premature Neonates is driven by SIRT1-Dependent Epigenetic Regulation of MKK6.
Périodique
Scientific reports
Auteur(s)
Simoncini S., Chateau A.L., Robert S., Todorova D., Yzydorzick C., Lacroix R., Ligi I., Louis L., Bachelier R., Simeoni U., Magdinier F., Dignat-George F., Sabatier F.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Statut éditorial
Publié
Date de publication
15/08/2017
Peer-reviewed
Oui
Volume
7
Numéro
1
Pages
8277
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
Senescent cells may exert detrimental effect on microenvironment through the secretion of soluble factors and the release of extracellular vesicles, such as microparticles, key actors in ageing and cardiovascular diseases. We previously reported that sirtuin-1 (SIRT1) deficiency drives accelerated senescence and dysfunction of endothelial colony-forming cells (ECFC) in PT neonates. Because preterm birth (PT) increases the risk for cardiovascular diseases during neonatal period as well as at adulthood, we hypothesized that SIRT1 deficiency could control the biogenesis of microparticles as part of a senescence-associated secretory phenotype (SASP) of PT-ECFC and investigated the related molecular mechanisms. Compared to control ECFC, PT-ECFC displayed a SASP associated with increased release of endothelial microparticles (EMP), mediating a paracrine induction of senescence in naïve endothelial cells. SIRT1 level inversely correlated with EMP release and drives PT-ECFC vesiculation. Global transcriptomic analysis revealed changes in stress response pathways, specifically the MAPK pathway. We delineate a new epigenetic mechanism by which SIRT1 deficiency regulates MKK6/p38 <sup>MAPK</sup> /Hsp27 pathway to promote EMP biogenesis in senescent ECFC. These findings deepen our understanding of the role of ECFC senescence in the disruption of endothelial homeostasis and provide potential new targets towards the control of cardiovascular risk in individuals born preterm.
Mots-clé
Cell-Derived Microparticles/metabolism, Cellular Senescence, Endothelial Cells/metabolism, Endothelial Progenitor Cells/metabolism, Epigenesis, Genetic, Gene Deletion, Gene Expression Profiling, Gene Expression Regulation, Humans, Infant, Newborn, MAP Kinase Kinase 6/genetics, Models, Biological, Paracrine Communication, Premature Birth, Signal Transduction, Sirtuin 1/genetics, Sirtuin 1/metabolism, Transcriptome, p38 Mitogen-Activated Protein Kinases/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
06/09/2017 11:12
Dernière modification de la notice
20/08/2019 15:53
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