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

Cellular senescence DNMT1 SIRT1 extracellular vesicles microRNAs

Journal

Journal of extracellular vesicles
ISSN: 2001-3078
Titre abrégé: J Extracell Vesicles
Pays: United States
ID NLM: 101610479

Informations de publication

Date de publication:
2020
Historique:
received: 10 08 2019
revised: 26 01 2020
accepted: 29 01 2020
entrez: 12 3 2020
pubmed: 12 3 2020
medline: 12 3 2020
Statut: epublish

Résumé

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.

Identifiants

pubmed: 32158519
doi: 10.1080/20013078.2020.1725285
pii: 1725285
pmc: PMC7048230
doi:

Types de publication

Journal Article

Langues

eng

Pagination

1725285

Informations de copyright

© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles.

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Auteurs

Emanuela Mensà (E)

Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy.

Michele Guescini (M)

Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.

Angelica Giuliani (A)

Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy.

Maria Giulia Bacalini (MG)

IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.

Deborah Ramini (D)

Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy.

Giacomo Corleone (G)

Department of Surgery and Cancer, Imperial College London, London, UK.

Manuela Ferracin (M)

Department of Experimental, Diagnostic, and Specialty Medicine, University of Bologna, Bologna, Italy.

Gianluca Fulgenzi (G)

Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy.

Laura Graciotti (L)

Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy.

Leonardo Sorci (L)

Department of Materials, Environmental Sciences and Urban Planning, Università Politecnica delle Marche, Ancona, Italy.

Michela Battistelli (M)

Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.

Vladia Monsurrò (V)

Department of Medicine, University of Verona, Verona, Italy.

Anna Rita Bonfigli (AR)

Scientific Direction, IRCCS INRCA, Ancona, Italy.

Maurizio Cardelli (M)

Advanced Technology Center for Aging Research, Scientific Technological Area, IRCCS INRCA, Ancona, Italy.

Rina Recchioni (R)

Center of Clinical Pathology and Innovative Therapy, IRCCS INRCA, Ancona, Italy.

Fiorella Marcheselli (F)

Center of Clinical Pathology and Innovative Therapy, IRCCS INRCA, Ancona, Italy.

Silvia Latini (S)

Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy.

Serena Maggio (S)

Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.

Mirco Fanelli (M)

Department of Biomolecular Sciences, Molecular Pathology Laboratory "Paola", University of Urbino Carlo Bo, Fano, Italy.

Stefano Amatori (S)

Department of Biomolecular Sciences, Molecular Pathology Laboratory "Paola", University of Urbino Carlo Bo, Fano, Italy.

Gianluca Storci (G)

Department of Experimental, Diagnostic, and Specialty Medicine, University of Bologna, Bologna, Italy.

Antonio Ceriello (A)

IRCCS MultiMedica, Milano, Italy.

Vilberto Stocchi (V)

Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.

Maria De Luca (M)

Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, USA.

Luca Magnani (L)

Department of Surgery and Cancer, Imperial College London, London, UK.

Maria Rita Rippo (MR)

Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy.

Antonio Domenico Procopio (AD)

Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy.
Center of Clinical Pathology and Innovative Therapy, IRCCS INRCA, Ancona, Italy.

Claudia Sala (C)

Department of Physics and Astronomy, University of Bologna, Bologna, Italy.

Iva Budimir (I)

Department of Physics and Astronomy, University of Bologna, Bologna, Italy.

Cristian Bassi (C)

Department of Morphology, Surgery & Experimental Medicine, and Laboratory for the Technologies of Advanced Therapies, Tecnopolo, University of Ferrara, Ferrara, Italy.

Massimo Negrini (M)

Department of Morphology, Surgery & Experimental Medicine, and Laboratory for the Technologies of Advanced Therapies, Tecnopolo, University of Ferrara, Ferrara, Italy.

Paolo Garagnani (P)

Department of Experimental, Diagnostic, and Specialty Medicine, University of Bologna, Bologna, Italy.
Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden.
Personal Genomics S.r.l., Verona, Italy.

Claudio Franceschi (C)

IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia.

Jacopo Sabbatinelli (J)

Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy.

Massimiliano Bonafè (M)

Department of Experimental, Diagnostic, and Specialty Medicine, University of Bologna, Bologna, Italy.

Fabiola Olivieri (F)

Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy.
Center of Clinical Pathology and Innovative Therapy, IRCCS INRCA, Ancona, Italy.

Classifications MeSH