Impaired regeneration in LGMD2A supported by increased PAX7-positive satellite cell content and muscle-specific microrna dysregulation

Muscle Nerve. 2013 May;47(5):731-9. doi: 10.1002/mus.23669. Epub 2013 Mar 29.


Introduction: Recent in vitro studies suggest that CAPN3 deficiency leads initially to accelerated myofiber formation followed by depletion of satellite cells (SC). In normal muscle, up-regulation of miR-1 and miR-206 facilitates transition from proliferating SCs to differentiating myogenic progenitors.

Methods: We examined the histopathological stages, Pax7 SC content, and muscle-specific microRNA expression in biopsy specimens from well-characterized LGMD 2A patients to gain insight into disease pathogenesis.

Results: Three distinct stages of pathological changes were identified that represented the continuum of the dystrophic process from prominent inflammation with necrosis and regeneration to prominent fibrosis, which correlated with age and disease duration. Pax7-positive SCs were highest in the fibrotic group and correlated with down-regulation of miR-1, miR-133a, and miR-206.

Conclusions: These observations, and other published reports, are consistent with microRNA dysregulation leading to inability of Pax7-positive SCs to transit from proliferation to differentiation. This results in impaired regeneration and fibrosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cell Differentiation
  • Cell Proliferation
  • Child
  • Child, Preschool
  • Female
  • Fibrosis
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Muscular Dystrophies, Limb-Girdle / metabolism*
  • Muscular Dystrophies, Limb-Girdle / pathology
  • Muscular Dystrophies, Limb-Girdle / physiopathology
  • Myoblasts / metabolism
  • Myoblasts / pathology
  • PAX7 Transcription Factor / genetics
  • PAX7 Transcription Factor / metabolism*
  • Regeneration / physiology*
  • Satellite Cells, Skeletal Muscle / metabolism*
  • Satellite Cells, Skeletal Muscle / pathology


  • MicroRNAs
  • PAX7 Transcription Factor
  • PAX7 protein, human

Supplementary concepts

  • Limb-girdle muscular dystrophy type 2A