Muscle fiber atrophy and regeneration coexist in collagen VI-deficient human muscle

Role of calpain-3 and nuclear factor-κB signaling

Sonia Paco, Isidre Ferrer, Cristina Jou, Victoria Cusí, Joan Corbera, Ferran Torner, Francesca Gualandi, Patrizia Sabatelli, Anna Orozco, Anna Maria Gómez-Foix, Jaume Colomer, Andres Nascimento, Cecilia Jimenez-Mallebrera

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)894-906
Number of pages13
JournalJournal of Neuropathology and Experimental Neurology
Volume71
Issue number10
DOIs
Publication statusPublished - Oct 2012

Fingerprint

Calpain
Muscular Atrophy
Regeneration
Collagen
Muscles
Muscular Dystrophies
Muscular Diseases
Proteasome Endopeptidase Complex
Ubiquitin
Cell Size
Connective Tissue
Muscle Cells
Adipose Tissue
Cell Survival
Down-Regulation
Cell Count
Maintenance
RNA
Biopsy
Messenger RNA

Keywords

  • Calpain-3
  • Collagen type VI
  • Extracellular matrix
  • Muscle atrophy
  • Muscle regeneration
  • NF-κB
  • Ullrich congenital muscular dystrophy

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Muscle fiber atrophy and regeneration coexist in collagen VI-deficient human muscle : Role of calpain-3 and nuclear factor-κB signaling. / Paco, Sonia; Ferrer, Isidre; Jou, Cristina; Cusí, Victoria; Corbera, Joan; Torner, Ferran; Gualandi, Francesca; Sabatelli, Patrizia; Orozco, Anna; Gómez-Foix, Anna Maria; Colomer, Jaume; Nascimento, Andres; Jimenez-Mallebrera, Cecilia.

In: Journal of Neuropathology and Experimental Neurology, Vol. 71, No. 10, 10.2012, p. 894-906.

Research output: Contribution to journalArticle

Paco, S, Ferrer, I, Jou, C, Cusí, V, Corbera, J, Torner, F, Gualandi, F, Sabatelli, P, Orozco, A, Gómez-Foix, AM, Colomer, J, Nascimento, A & Jimenez-Mallebrera, C 2012, 'Muscle fiber atrophy and regeneration coexist in collagen VI-deficient human muscle: Role of calpain-3 and nuclear factor-κB signaling', Journal of Neuropathology and Experimental Neurology, vol. 71, no. 10, pp. 894-906. https://doi.org/10.1097/NEN.0b013e31826c6f7b
Paco, Sonia ; Ferrer, Isidre ; Jou, Cristina ; Cusí, Victoria ; Corbera, Joan ; Torner, Ferran ; Gualandi, Francesca ; Sabatelli, Patrizia ; Orozco, Anna ; Gómez-Foix, Anna Maria ; Colomer, Jaume ; Nascimento, Andres ; Jimenez-Mallebrera, Cecilia. / Muscle fiber atrophy and regeneration coexist in collagen VI-deficient human muscle : Role of calpain-3 and nuclear factor-κB signaling. In: Journal of Neuropathology and Experimental Neurology. 2012 ; Vol. 71, No. 10. pp. 894-906.
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