TY - JOUR
T1 - Small extracellular vesicles deliver miR-21 and miR-217 as pro-senescence effectors to endothelial cells
AU - Mensà, Emanuela
AU - Guescini, Michele
AU - Giuliani, Angelica
AU - Bacalini, Maria Giulia
AU - Ramini, Deborah
AU - Corleone, Giacomo
AU - Ferracin, Manuela
AU - Fulgenzi, Gianluca
AU - Graciotti, Laura
AU - Prattichizzo, Francesco
AU - Sorci, Leonardo
AU - Battistelli, Michela
AU - Monsurrò, Vladia
AU - Bonfigli, Anna Rita
AU - Cardelli, Maurizio
AU - Recchioni, Rina
AU - Marcheselli, Fiorella
AU - Latini, Silvia
AU - Maggio, Serena
AU - Fanelli, Mirco
AU - Amatori, Stefano
AU - Storci, Gianluca
AU - Ceriello, Antonio
AU - Stocchi, Vilberto
AU - De Luca, Maria
AU - Magnani, Luca
AU - Rippo, Maria Rita
AU - Procopio, Antonio Domenico
AU - Sala, Claudia
AU - Budimir, Iva
AU - Bassi, Cristian
AU - Negrini, Massimo
AU - Garagnani, Paolo
AU - Franceschi, Claudio
AU - Sabbatinelli, Jacopo
AU - Bonafè, Massimiliano
AU - Olivieri, Fabiola
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
KW - Cellular senescence
KW - DNMT1
KW - extracellular vesicles
KW - microRNAs
KW - SIRT1
UR - http://www.scopus.com/inward/record.url?scp=85079712793&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85079712793&partnerID=8YFLogxK
U2 - 10.1080/20013078.2020.1725285
DO - 10.1080/20013078.2020.1725285
M3 - Article
AN - SCOPUS:85079712793
VL - 9
JO - Journal of Extracellular Vesicles
JF - Journal of Extracellular Vesicles
SN - 2001-3078
IS - 1
M1 - 1725285
ER -