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

Xiomara Q. Rosales, Vinod Malik, Amita Sneh, Lei Chen, Sarah Lewis, Janaiah Kota, Julie M. Gastier-Foster, Caroline Astbury, Rob Pyatt, Shalini Reshmi, Louise R. Rodino-Klapac, K. Reed Clark, Jerry R. Mendell, Zarife Sahenk

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)731-739
Number of pages9
JournalMuscle and Nerve
Volume47
Issue number5
DOIs
StatePublished - May 1 2013

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Keywords

  • Fibrosis
  • LGMD2A
  • MicroRNA
  • Muscle regeneration
  • Pax

ASJC Scopus subject areas

  • Physiology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Physiology (medical)

Cite this

Rosales, X. Q., Malik, V., Sneh, A., Chen, L., Lewis, S., Kota, J., Gastier-Foster, J. M., Astbury, C., Pyatt, R., Reshmi, S., Rodino-Klapac, L. R., Clark, K. R., Mendell, J. R., & Sahenk, Z. (2013). Impaired regeneration in LGMD2A supported by increased PAX7-positive satellite cell content and muscle-specific microrna dysregulation. Muscle and Nerve, 47(5), 731-739. https://doi.org/10.1002/mus.23669