Small extracellular vesicles deliver miR-21 and miR-217 as pro-senescence effectors to endothelial cells.
Cellular senescence
DNMT1
SIRT1
extracellular vesicles
microRNAs
Journal
Journal of extracellular vesicles
ISSN: 2001-3078
Titre abrégé: J Extracell Vesicles
Pays: United States
ID NLM: 101610479
Informations de publication
Date de publication:
2020
2020
Historique:
received:
10
08
2019
revised:
26
01
2020
accepted:
29
01
2020
entrez:
12
3
2020
pubmed:
12
3
2020
medline:
12
3
2020
Statut:
epublish
Résumé
The role of epigenetics in endothelial cell senescence is a cutting-edge topic in ageing research. However, little is known of the relative contribution to pro-senescence signal propagation provided by microRNAs shuttled by extracellular vesicles (EVs) released from senescent cells. Analysis of microRNA and DNA methylation profiles in non-senescent (control) and senescent (SEN) human umbilical vein endothelial cells (HUVECs), and microRNA profiling of their cognate small EVs (sEVs) and large EVs demonstrated that SEN cells released a significantly greater sEV number than control cells. sEVs were enriched in miR-21-5p and miR-217, which target DNMT1 and SIRT1. Treatment of control cells with SEN sEVs induced a miR-21/miR-217-related impairment of DNMT1-SIRT1 expression, the reduction of proliferation markers, the acquisition of a senescent phenotype and a partial demethylation of the locus encoding for miR-21. MicroRNA profiling of sEVs from plasma of healthy subjects aged 40-100 years showed an inverse U-shaped age-related trend for miR-21-5p, consistent with senescence-associated biomarker profiles. Our findings suggest that miR-21-5p/miR-217 carried by SEN sEVs spread pro-senescence signals, affecting DNA methylation and cell replication.
Identifiants
pubmed: 32158519
doi: 10.1080/20013078.2020.1725285
pii: 1725285
pmc: PMC7048230
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1725285Informations de copyright
© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles.
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