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.
Small extracellular vesicles deliver miR-21 and miR-217 as pro-senescence effectors to endothelial cells / Mensa E.; Guescini M.; Giuliani A.; Bacalini M.G.; Ramini D.; Corleone G.; Ferracin M.; Fulgenzi G.; Graciotti L.; Prattichizzo F.; Sorci L.; Battistelli M.; Monsurro V.; Bonfigli A.R.; Cardelli M.; Recchioni R.; Marcheselli F.; Latini S.; Maggio S.; Fanelli M.; Amatori S.; Storci G.; Ceriello A.; Stocchi V.; De Luca M.; Magnani L.; Rippo M.R.; Procopio A.D.; Sala C.; Budimir I.; Bassi C.; Negrini M.; Garagnani P.; Franceschi C.; Sabbatinelli J.; Bonafe M.; Olivieri F.. - In: JOURNAL OF EXTRACELLULAR VESICLES. - ISSN 2001-3078. - ELETTRONICO. - 9:1(2020), pp. 1725285-1725285. [10.1080/20013078.2020.1725285]
Small extracellular vesicles deliver miR-21 and miR-217 as pro-senescence effectors to endothelial cells
Bacalini M. G.;Ferracin M.;Fulgenzi G.;Graciotti L.;Maggio S.;Storci G.;Sala C.;Budimir I.;Bassi C.;Garagnani P.;Franceschi C.;Bonafe M.;
2020
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.| File | Dimensione | Formato | |
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