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

被引：132

作者：

Mensa, Emanuela ^{[1
]}

Guescini, Michele ^{[2
]}

Giuliani, Angelica ^{[1
]}

Bacalini, Maria Giulia ^{[3
]}

Ramini, Deborah ^{[1
]}

Corleone, Giacomo ^{[4
]}

Ferracin, Manuela ^{[5
]}

Fulgenzi, Gianluca ^{[1
]}

Graciotti, Laura ^{[1
]}

Prattichizzo, Francesco ^{[6
]}

Sorci, Leonardo ^{[7
]}

Battistelli, Michela ^{[2
]}

Monsurro, Vladia ^{[8
]}

Bonfigli, Anna Rita ^{[9
]}

Cardelli, Maurizio ^{[10
]}

Recchioni, Rina ^{[11
]}

Marcheselli, Fiorella ^{[11
]}

Latini, Silvia ^{[1
]}

Maggio, Serena ^{[2
]}

Fanelli, Mirco ^{[12
]}

Amatori, Stefano ^{[12
]}

Storci, Gianluca ^{[5
]}

Ceriello, Antonio ^{[6
]}

Stocchi, Vilberto ^{[2
]}

De Luca, Maria ^{[13
]}

Magnani, Luca ^{[4
]}

Rippo, Maria Rita ^{[1
]}

Procopio, Antonio Domenico ^{[1
,11
]}

Sala, Claudia ^{[14
]}

Budimir, Iva ^{[14
]}

Bassi, Cristian ^{[15
,16
]}

Negrini, Massimo ^{[15
,16
]}

Garagnani, Paolo ^{[5
,17
,18
]}

Franceschi, Claudio ^{[3
,19
]}

Sabbatinelli, Jacopo ^{[1
]}

Bonafe, Massimiliano ^{[5
]}

Olivieri, Fabiola ^{[1
,11
]}

机构：

[1] Univ Politecn Marche, Dept Clin & Mol Sci, Via Tronto 10-A, Ancona, Italy

[2] Univ Urbino Carlo Bo, Dept Biomol Sci, Urbino, Italy

[3] IRCCS Ist Sci Neurol Bologna, Bologna, Italy

[4] Imperial Coll London, Dept Surg & Canc, London, England

[5] Univ Bologna, Dept Expt Diagnost & Specialty Med, Bologna, Italy

[6] IRCCS MultiMed, Milan, Italy

[7] Univ Politecn Marche, Dept Mat Environm Sci & Urban Planning, Ancona, Italy

[8] Univ Verona, Dept Med, Verona, Italy

[9] IRCCS INRCA, Sci Direct, Ancona, Italy

[10] IRCCS INRCA, Adv Technol Ctr Aging Res, Sci Technol Area, Ancona, Italy

[11] IRCCS INRCA, Ctr Clin Pathol & Innovat Therapy, Ancona, Italy

[12] Univ Urbino Carlo Bo, Dept Biomol Sci, Mol Pathol Lab Paola, Fano, Italy

[13] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA

[14] Univ Bologna, Dept Phys & Astron, Bologna, Italy

[15] Univ Ferrara, Dept Morphol Surg & Expt Med, Tecnopolo, Ferrara, Italy

[16] Univ Ferrara, Lab Technol Adv Therapies, Tecnopolo, Ferrara, Italy

[17] Karolinska Inst, Dept Lab Med, Clin Chem, Huddinge Univ Hosp, Stockholm, Sweden

[18] Personal Genom Srl, Verona, Italy

[19] Lobachevsky State Univ Nizhny Novgorod, Nizhnii Novgorod, Russia

来源：

JOURNAL OF EXTRACELLULAR VESICLES | 2020年 / 9卷 / 01期

关键词：

Cellular senescence; microRNAs; DNMT1; SIRT1; extracellular vesicles; CELLULAR SENESCENCE; DNA; MICRORNAS; EXOSOMES; CANCER; PERSPECTIVE; MECHANISMS; EXPRESSION; CONTRIBUTE; MARKER;

D O I：

10.1080/20013078.2020.1725285

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：23

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