HDAC inhibitors tune miRNAs in extracellular vesicles of dystrophic muscle-resident mesenchymal cells
| Autor: | Marina Bouché, Tucciarone L, Martina Sandoná, Adele D'Amico, Manuel Scimeca, Enrico Bertini, Pier Lorenzo Puri, Valentina Saccone, Sara Cazzaniga, Antonella Bongiovanni, Valentina Buffa, Paolo Bettica, Marco De Bardi, Silvia Consalvi, Daniela F. Angelini |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Duchenne muscular dystrophy Inflammation Biochemistry 03 medical and health sciences Mice 0302 clinical medicine HDAC inhibitors Fibrosis Genetics medicine Animals Humans Settore BIO/13 - BIOLOGIA APPLICATA Muscle Skeletal Molecular Biology duchenne muscular dystrophy 030304 developmental biology 0303 health sciences muscle regeneration microRNA Chemistry Regeneration (biology) Mesenchymal stem cell Articles medicine.disease Cell biology Transplantation Histone Deacetylase Inhibitors Mice Inbred C57BL MicroRNAs Mice Inbred mdx medicine.symptom Stem cell extracellular vesicles 030217 neurology & neurosurgery Ex vivo |
| Zdroj: | EMBO reports 21 (2020). doi:10.15252/embr.202050863 info:cnr-pdr/source/autori:Sandonà Martina; Consalvi Silvia; Tucciarone Luca; De Bardi Marco; Scimeca Manuel; Angelini Daniela Francesca; Buffa Valentina; D'Amico Adele; Bertini Enrico Silvio; Cazzaniga Sara; Bettica Paolo; Bouché Marina; Bongiovanni Antonella; Puri Pier Lorenzo; Saccone Valentina;/titolo:HDAC inhibitors tune miRNAs in extracellular vesicles of dystrophic muscle-resident mesenchymal cells/doi:10.15252%2Fembr.202050863/rivista:EMBO reports (Print)/anno:2020/pagina_da:/pagina_a:/intervallo_pagine:/volume:21 EMBO Rep |
| DOI: | 10.15252/embr.202050863 |
| Popis: | We show that extracellular vesicles (EVs) released by mesenchymal cells (i.e., fibro-adipogenic progenitors--FAPs) mediate microRNA (miR) transfer to muscle stem cells (MuSCs) and that exposure of dystrophic FAPs to HDAC inhibitors (HDACis) increases the intra-EV levels of a subset of miRs, which cooperatively target biological processes of therapeutic interest, including regeneration, fibrosis, and inflammation. Increased levels of miR-206 in EVs released by FAPs of muscles from Duchenne muscular dystrophy (DMD) patients or mdx mice exposed to HDACi are associated with enhanced regeneration and decreased fibrosis. Consistently, EVs from HDACi-treated dystrophic FAPs can stimulate MuSC activation and expansion ex vivo, and promote regeneration, while inhibiting fibrosis and inflammation of dystrophic muscles, upon intramuscular transplantation in mdx mice, in vivo. AntagomiR-mediated blockade of individual miRs reveals a specific requirement of miR-206 for EV-induced expansion of MuSCs and regeneration of dystrophic muscles, and indicates that cooperative activity of HDACi-induced miRs accounts for the net biological effect of these EVs. These data point to pharmacological modulation of EV content as novel strategy for therapeutic interventions in muscular dystrophies. |
| Databáze: | OpenAIRE |
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