title: Autophagy regulates satellite cell ability to regenerate normal and dystrophic muscles.
abstract: Autophagy is emerging as a key regulatory process during skeletal muscle development, regeneration and homeostasis, and deregulated autophagy has been implicated in muscular disorders and age-related muscle decline. We have monitored autophagy in muscles of mdx mice and human Duchenne muscular dystrophy (DMD) patients at different stages of disease. Our data show that autophagy is activated during the early, compensatory regenerative stages of DMD. A progressive reduction was observed during mdx disease progression, in coincidence with the functional exhaustion of satellite cell-mediated regeneration and accumulation of fibrosis. Moreover, pharmacological manipulation of autophagy can influence disease progression in mdx mice. Of note, studies performed in regenerating muscles of wild-type mice revealed an essential role of autophagy in the activation of satellite cells upon muscle injury. These results support the notion that regeneration-associated autophagy contributes to the early compensatory stage of DMD progression, and interventions that extend activation of autophagy might be beneficial in the treatment of DMD. Thus, autophagy could be a 'disease modifier' targeted by interventions aimed to promote regeneration and delay disease progression in DMD.
authors.affiliation: Laboratory of Epigenetic and Regenerative Pharmacology, IRCCS Fondazione Santa Lucia, Rome, Italy.|Department of Medicine, Institute of Translational Pharmacology, National Research Council of Italy, Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Fiacco
authors.affiliation: Laboratory of Epigenetic and Regenerative Pharmacology, IRCCS Fondazione Santa Lucia, Rome, Italy.|Department of Medicine, Institute of Translational Pharmacology, National Research Council of Italy, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Castagnetti
authors.affiliation: Laboratory of Epigenetic and Regenerative Pharmacology, IRCCS Fondazione Santa Lucia, Rome, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Bianconi
authors.affiliation: Laboratory of Epigenetic and Regenerative Pharmacology, IRCCS Fondazione Santa Lucia, Rome, Italy.|Department of Life Sciences, Cell Biology and Neurobiology Institute, National Research Council of Italy, Roma, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Madaro
authors.affiliation: Laboratory of Epigenetic and Regenerative Pharmacology, IRCCS Fondazione Santa Lucia, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: De Bardi
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy.|Department of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Nazio
authors.affiliation: Unit of Neuromuscular and Neurodegenerative Disorders, Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: D'Amico
authors.affiliation: Unit of Neuromuscular and Neurodegenerative Disorders, Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Bertini
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy.|Unit of Cell Stress and Survival, Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: F
authors.initials: F
authors.lastname: Cecconi
authors.affiliation: Laboratory of Epigenetic and Regenerative Pharmacology, IRCCS Fondazione Santa Lucia, Rome, Italy.|Muscle Development and Regeneration Program, Sanford Children's Health Research Center, Sanford Prebys Burnham Medical Discovery Institute, La Jolla, CA 92037, USA.
authors.forename: P L
authors.initials: PL
authors.lastname: Puri
authors.affiliation: Laboratory of Epigenetic and Regenerative Pharmacology, IRCCS Fondazione Santa Lucia, Rome, Italy.|Department of Medicine, Institute of Translational Pharmacology, National Research Council of Italy, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Latella
mesh_terms: D000818:Animals; D001343:Autophagy; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000473:pathology* / Q000503:physiopathology*; D009137:Muscular Dystrophy, Animal / Q000473:pathology / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000473:pathology* / Q000503:physiopathology*; D012038:Regeneration; D032496:Satellite Cells, Skeletal Muscle / Q000473:pathology*