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

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

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

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  • Cite this

    Paco, S., Ferrer, I., Jou, C., Cusí, V., Corbera, J., Torner, F., Gualandi, F., Sabatelli, P., Orozco, A., Gómez-Foix, A. M., 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, 71(10), 894-906. https://doi.org/10.1097/NEN.0b013e31826c6f7b