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

Abstract 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 acce...

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Autores principales:	Stéphanie Simoncini, Anne-Line Chateau, Stéphane Robert, Dilyana Todorova, Catherine Yzydorzick, Romaric Lacroix, Isabelle Ligi, Laurence Louis, Richard Bachelier, Umberto Simeoni, Frédérique Magdinier, Françoise Dignat-George, Florence Sabatier
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4c107dc93a564daf8a97cf91c02ff34f
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spelling	oai:doaj.org-article:4c107dc93a564daf8a97cf91c02ff34f2021-12-02T15:06:20ZBiogenesis of Pro-senescent Microparticles by Endothelial Colony Forming Cells from Premature Neonates is driven by SIRT1-Dependent Epigenetic Regulation of MKK610.1038/s41598-017-08883-12045-2322https://doaj.org/article/4c107dc93a564daf8a97cf91c02ff34f2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08883-1https://doaj.org/toc/2045-2322Abstract 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/p38MAPK/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.Stéphanie SimonciniAnne-Line ChateauStéphane RobertDilyana TodorovaCatherine YzydorzickRomaric LacroixIsabelle LigiLaurence LouisRichard BachelierUmberto SimeoniFrédérique MagdinierFrançoise Dignat-GeorgeFlorence SabatierNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stéphanie Simoncini Anne-Line Chateau Stéphane Robert Dilyana Todorova Catherine Yzydorzick Romaric Lacroix Isabelle Ligi Laurence Louis Richard Bachelier Umberto Simeoni Frédérique Magdinier Françoise Dignat-George Florence Sabatier Biogenesis of Pro-senescent Microparticles by Endothelial Colony Forming Cells from Premature Neonates is driven by SIRT1-Dependent Epigenetic Regulation of MKK6
description	Abstract 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/p38MAPK/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.
format	article
author	Stéphanie Simoncini Anne-Line Chateau Stéphane Robert Dilyana Todorova Catherine Yzydorzick Romaric Lacroix Isabelle Ligi Laurence Louis Richard Bachelier Umberto Simeoni Frédérique Magdinier Françoise Dignat-George Florence Sabatier
author_facet	Stéphanie Simoncini Anne-Line Chateau Stéphane Robert Dilyana Todorova Catherine Yzydorzick Romaric Lacroix Isabelle Ligi Laurence Louis Richard Bachelier Umberto Simeoni Frédérique Magdinier Françoise Dignat-George Florence Sabatier
author_sort	Stéphanie Simoncini
title	Biogenesis of Pro-senescent Microparticles by Endothelial Colony Forming Cells from Premature Neonates is driven by SIRT1-Dependent Epigenetic Regulation of MKK6
title_short	Biogenesis of Pro-senescent Microparticles by Endothelial Colony Forming Cells from Premature Neonates is driven by SIRT1-Dependent Epigenetic Regulation of MKK6
title_full	Biogenesis of Pro-senescent Microparticles by Endothelial Colony Forming Cells from Premature Neonates is driven by SIRT1-Dependent Epigenetic Regulation of MKK6
title_fullStr	Biogenesis of Pro-senescent Microparticles by Endothelial Colony Forming Cells from Premature Neonates is driven by SIRT1-Dependent Epigenetic Regulation of MKK6
title_full_unstemmed	Biogenesis of Pro-senescent Microparticles by Endothelial Colony Forming Cells from Premature Neonates is driven by SIRT1-Dependent Epigenetic Regulation of MKK6
title_sort	biogenesis of pro-senescent microparticles by endothelial colony forming cells from premature neonates is driven by sirt1-dependent epigenetic regulation of mkk6
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/4c107dc93a564daf8a97cf91c02ff34f
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Biogenesis of Pro-senescent Microparticles by Endothelial Colony Forming Cells from Premature Neonates is driven by SIRT1-Dependent Epigenetic Regulation of MKK6

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