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- Title
Small extracellular vesicles deliver miR-21 and miR-217 as pro-senescence effectors to endothelial cells.
- Authors
Mensà, Emanuela; Guescini, Michele; Giuliani, Angelica; Bacalini, Maria Giulia; Ramini, Deborah; Corleone, Giacomo; Ferracin, Manuela; Fulgenzi, Gianluca; Graciotti, Laura; Prattichizzo, Francesco; Sorci, Leonardo; Battistelli, Michela; Monsurrò, Vladia; Bonfigli, Anna Rita; Cardelli, Maurizio; Recchioni, Rina; Marcheselli, Fiorella; Latini, Silvia; Maggio, Serena; Fanelli, Mirco
- Abstract
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.
- Subjects
EXTRACELLULAR vesicles; ENDOTHELIAL cells; CELLULAR aging; DNA analysis; MICRORNA; EXOSOMES; EPIGENETICS
- Publication
Journal of Extracellular Vesicles, 2020, Vol 9, Issue 1, p1
- ISSN
2001-3078
- Publication type
Article
- DOI
10.1080/20013078.2020.1725285