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. - 9:1(2020), p. 1725285. [10.1080/20013078.2020.1725285]

Small extracellular vesicles deliver miR-21 and miR-217 as pro-senescence effectors to endothelial cells

Mensa E.;Giuliani A.;Ramini D.;Fulgenzi G.;Graciotti L.;Prattichizzo F.;Sorci L.;Latini S.;Rippo M. R.;Procopio A. D.;Sabbatinelli J.
;
Olivieri F.
2020-01-01

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.
2020
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11566/275020
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