title: Muscle-specific microRNA-206 targets multiple components in dystrophic skeletal muscle representing beneficial adaptations.
abstract: Over the last several years, converging lines of evidence have indicated that miR-206 plays a pivotal role in promoting muscle differentiation and regeneration, thereby potentially impacting positively on the progression of neuromuscular disorders, including Duchenne muscular dystrophy (DMD). Despite several studies showing the regulatory function of miR-206 on target mRNAs in skeletal muscle cells, the effects of overexpression of miR-206 in dystrophic muscles remain to be established. Here, we found that miR-206 overexpression in mdx mouse muscles simultaneously targets multiple mRNAs and proteins implicated in satellite cell differentiation, muscle regeneration, and at the neuromuscular junction. Overexpression of miR-206 also increased the levels of several muscle-specific mRNAs/proteins, while enhancing utrophin A expression at the sarcolemma. Finally, we also observed that the increased expression of miR-206 in dystrophin-deficient mouse muscle decreased the production of proinflammatory cytokines and infiltration of macrophages. Taken together, our results show that miR-206 acts as a pleiotropic regulator that targets multiple key mRNAs and proteins expected to provide beneficial adaptations in dystrophic muscle, thus highlighting its therapeutic potential for DMD.
authors.affiliation: Laboratoire Interuniversitaire de Biologie de la Motricité, Université de Saint Etienne, Université de Lyon, Lyon, France.|Department of Cellular and Molecular Medicine and Centre for Neuromuscular Disease, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; and.
authors.forename: Adel
authors.initials: A
authors.lastname: Amirouche
authors.affiliation: Laboratoire Interuniversitaire de Biologie de la Motricité, Université de Saint Etienne, Université de Lyon, Lyon, France.
authors.forename: Vanessa E
authors.initials: VE
authors.lastname: Jahnke
authors.affiliation: Department of Cellular and Molecular Medicine and Centre for Neuromuscular Disease, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; and.
authors.forename: John A
authors.initials: JA
authors.lastname: Lunde
authors.affiliation: Institut de Recherche Biomédicale des Armées, Département Environnements Opérationnels, Bretigny-sur-Orge, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Koulmann
authors.affiliation: Laboratoire Interuniversitaire de Biologie de la Motricité, Université de Saint Etienne, Université de Lyon, Lyon, France.
authors.forename: Damien G
authors.initials: DG
authors.lastname: Freyssenet
authors.affiliation: Department of Cellular and Molecular Medicine and Centre for Neuromuscular Disease, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; and jasmin@uottawa.ca.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Jasmin
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D005786:Gene Expression Regulation; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D014018:Tissue Distribution
chemical_list: D016207:Cytokines; D009124:Muscle Proteins
keywords: Duchenne muscular dystrophy; Pax7; miR-206; neuromuscular disease; neuromuscular junction; regeneration; therapy; utrophin