title: Elevated Expression of Moesin in Muscular Dystrophies.
abstract: Fibrosis is the main complication of muscular dystrophies. We identified moesin, a member of the ezrin-radixin-moesin family, in dystrophic muscles of mice representing Duchenne and congenital muscular dystrophies (DMD and CMD, respectively) and dysferlinopathy, but not in the wild type. High levels of moesin were also observed in muscle biopsy specimens from DMD, Ullrich CMD, and merosin-deficient CMD patients, all of which present high levels of fibrosis. The myofibroblasts, responsible for extracellular matrix protein synthesis, and the macrophages infiltrating the dystrophic muscles were the source of moesin. Moesin-positive cells were embedded within the fibrotic areas between the myofibers adjacent to the collagen type I fibers. Radixin was also synthesized by the myofibroblasts, whereas ezrin colocalized with the myofiber membranes. In animal models and patients' muscles, part of the moesin was in its active phosphorylated form. Inhibition of fibrosis by halofuginone, an antifibrotic agent, resulted in a major decrease in moesin levels in the muscles of DMD and CMD mice. In summary, the results of this study may pave the way for exploiting moesin as a novel target for intervention in MDs, and as part of a battery of biomarkers to evaluate treatment success in preclinical studies and clinical trials.
authors.affiliation: Institute of Animal Sciences, Volcani Center, Bet Dagan, Israel. Electronic address: mark.pines@mail.huji.ac.il.
authors.forename: Mark
authors.initials: M
authors.lastname: Pines
authors.affiliation: Institute of Animal Sciences, Volcani Center, Bet Dagan, Israel.
authors.forename: Oshrat
authors.initials: O
authors.lastname: Levi
authors.affiliation: Institute of Animal Sciences, Volcani Center, Bet Dagan, Israel.
authors.forename: Olga
authors.initials: O
authors.lastname: Genin
authors.affiliation: Institute of Animal Sciences, Volcani Center, Bet Dagan, Israel; Department of Animal Sciences, the Hebrew University of Jerusalem, Rehovot, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Lavy
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Ospedale S. Camillo, Venice, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Angelini
authors.affiliation: Research Center in Myology, UPMC Univ Paris 06-Inserm Unité Mixte de Recherche en Santé 974, Centre National de la Recherche Scientifique Formation de Recherche en Evolution 3617, Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Allamand
authors.affiliation: Department of Animal Sciences, the Hebrew University of Jerusalem, Rehovot, Israel.
authors.forename: Orna
authors.initials: O
authors.lastname: Halevy
mesh_terms: D000328:Adult; D000818:Animals; D002648:Child; D002675:Child, Preschool; D024042:Collagen Type I / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003964:Diaphragm / Q000187:drug effects / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D008840:Microfilament Proteins; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009136:Muscular Dystrophies / Q000378:metabolism* / Q000473:pathology; D058628:Myofibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D052999:Quinazolinones / Q000494:pharmacology
chemical_list: D024042:Collagen Type I; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D010880:Piperidines; D052999:Quinazolinones; C071058:moesin; C071776:radixin; C010176:halofuginone