Small extracellular vesicles deliver miR-21 and miR-217 as pro-senescence effectors to endothelial cells. Issue 1 (1st January 2020)

• Record Type: Journal Article
• 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; Amatori, Stefano; Storci, Gianluca; Ceriello, Antonio; Stocchi, Vilberto; De Luca, Maria; Magnani, Luca; Rippo, Maria Rita; Procopio, Antonio Domenico; Sala, Claudia; Budimir, Iva; Bassi, Cristian; Negrini, Massimo; Garagnani, Paolo; Franceschi, Claudio; Sabbatinelli, Jacopo; Bonafè, Massimiliano; Olivieri, Fabiola;
• Is Part Of: Journal of extracellular vesicles. Volume 9:Issue 1(2020)
• Publication Date: 2020-01-01
• Subjects: Cellular senescence -- microRNAs -- DNMT1 -- SIRT1 -- extracellular vesicles; Cells -- Mechanical properties -- Periodicals; Transport Vesicles; Cells -- Mechanical properties; Periodicals; Fulltext; Internet Resources; Periodicals; Electronic journals; Periodicals; 571.63
• DOI: 10.1080/20013078.2020.1725285
• Languages: English
• ISSNs: 2001-3078

Abstract

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.