title: Muscle fiber atrophy and regeneration coexist in collagen VI-deficient human muscle: role of calpain-3 and nuclear factor-κB signaling.
abstract: Ullrich congenital muscular dystrophy (UCMD) is a common form of muscular dystrophy associated with defects in collagen VI. It is characterized by loss of individual muscle fibers and muscle mass and proliferation of connective and adipose tissues. We sought to investigate the mechanisms by which collagen VI regulates muscle cell survival, size, and regeneration and, in particular, the potential role of the ubiquitin-proteasome and calpain-proteolytic systems. We studied muscle biopsies of UCMD (n = 6), other myopathy (n = 12), and control patients (n = 10) and found reduced expression of atrogin-1, MURF1, and calpain-3 mRNAs in UCMD cases. Downregulation of calpain-3 was associated with changes in the nuclear immunolocalization of nuclear factor-κB. We also observed increased expression versus controls of regeneration markers at the protein and RNA levels. Satellite cell numbers did not differ in collagen VI-deficient muscle versus normal nonregenerating muscle, indicating that collagen VI does not play a key role in the maintenance of the satellite cell pool. Our results indicate that alterations in calpain-3 and nuclear factor-κB signaling pathways may contribute to muscle mass loss in UCMD muscle, whereas atrogin-1 and MURF1 are not likely to play a major role.
authors.affiliation: Neuromuscular Unit, Neurology Department, Fundación Sant Joan de Déu, Hospital Materno-Infantil Sant Joan de Déu, Barcelona, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Paco
authors.forename: Isidre
authors.initials: I
authors.lastname: Ferrer
authors.forename: Cristina
authors.initials: C
authors.lastname: Jou
authors.forename: Victoria
authors.initials: V
authors.lastname: Cusí
authors.forename: Joan
authors.initials: J
authors.lastname: Corbera
authors.forename: Ferran
authors.initials: F
authors.lastname: Torner
authors.forename: Francesca
authors.initials: F
authors.lastname: Gualandi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Sabatelli
authors.forename: Anna
authors.initials: A
authors.lastname: Orozco
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Gómez-Foix
authors.forename: Jaume
authors.initials: J
authors.lastname: Colomer
authors.forename: Andres
authors.initials: A
authors.lastname: Nascimento
authors.forename: Cecilia
authors.initials: C
authors.lastname: Jimenez-Mallebrera
mesh_terms: D002154:Calpain / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D024142:Collagen Type VI / Q000172:deficiency*; D005260:Female; D006801:Humans; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000473:pathology / Q000502:physiology*; D009124:Muscle Proteins / Q000502:physiology*; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology; D009133:Muscular Atrophy / Q000378:metabolism* / Q000473:pathology; D009136:Muscular Dystrophies / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D055815:Young Adult
chemical_list: D024142:Collagen Type VI; D009124:Muscle Proteins; D016328:NF-kappa B; C105884:CAPN3 protein, human; D002154:Calpain