title: Common micro-RNA signature in skeletal muscle damage and regeneration induced by Duchenne muscular dystrophy and acute ischemia.
abstract: The aim of this work was to identify micro-RNAs (miRNAs) involved in the pathological pathways activated in skeletal muscle damage and regeneration by both dystrophin absence and acute ischemia. Eleven miRNAs were deregulated both in MDX mice and in Duchenne muscular dystrophy patients (DMD signature). Therapeutic interventions ameliorating the mdx-phenotype rescued DMD-signature alterations. The significance of DMD-signature changes was characterized using a damage/regeneration mouse model of hind-limb ischemia and newborn mice. According to their expression, DMD-signature miRNAs were divided into 3 classes. 1) Regeneration miRNAs, miR-31, miR-34c, miR-206, miR-335, miR-449, and miR-494, which were induced in MDX mice and in DMD patients, but also in newborn mice and in newly formed myofibers during postischemic regeneration. Notably, miR-206, miR-34c, and miR-335 were up-regulated following myoblast differentiation in vitro. 2) Degenerative-miRNAs, miR-1, miR-29c, and miR-135a, that were down-modulated in MDX mice, in DMD patients, in the degenerative phase of the ischemia response, and in newborn mice. Their down-modulation was linked to myofiber loss and fibrosis. 3) Inflammatory miRNAs, miR-222 and miR-223, which were expressed in damaged muscle areas, and their expression correlated with the presence of infiltrating inflammatory cells. These findings show an important role of miRNAs in physiopathological pathways regulating muscle response to damage and regeneration.
authors.affiliation: Istituto Di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, San Donato Milanese, Milan, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Greco
authors.forename: Marco
authors.initials: M
authors.lastname: De Simone
authors.forename: Claudia
authors.initials: C
authors.lastname: Colussi
authors.forename: Germana
authors.initials: G
authors.lastname: Zaccagnini
authors.forename: Pasquale
authors.initials: P
authors.lastname: Fasanaro
authors.forename: Mario
authors.initials: M
authors.lastname: Pescatori
authors.forename: Rosanna
authors.initials: R
authors.lastname: Cardani
authors.forename: Riccardo
authors.initials: R
authors.lastname: Perbellini
authors.forename: Eleonora
authors.initials: E
authors.lastname: Isaia
authors.forename: Patrizio
authors.initials: P
authors.lastname: Sale
authors.forename: Giovanni
authors.initials: G
authors.lastname: Meola
authors.forename: Maurizio C
authors.initials: MC
authors.lastname: Capogrossi
authors.forename: Carlo
authors.initials: C
authors.lastname: Gaetano
authors.forename: Fabio
authors.initials: F
authors.lastname: Martelli
mesh_terms: D000818:Animals; D006801:Humans; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018101:Mice, Inbred mdx; D035683:MicroRNAs / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism* / Q000473:pathology; D012038:Regeneration
chemical_list: D035683:MicroRNAs