Gene Expression Profiling in Limb-Girdle Muscular Dystrophy 2A

Sáenz, Amets and Azpitarte, Margarita and Armañanzas Arnedillo, Ruben and Leturcq, France and Alzualde, Ainhoa and Inza Cano, Iñaki and García Bragado, Federico and Herran, Gaspar de la and Corcuera, Julian and Cabello, Ana and Navarro, Carmen and Torre, Carolina de la and Gallardo, Eduard and Illa, Isabel and López de Munain, Adolfo (2008). Gene Expression Profiling in Limb-Girdle Muscular Dystrophy 2A. "Plos One", v. 3 (n. 11); pp. 1-14. ISSN 1932-6203.


Title: Gene Expression Profiling in Limb-Girdle Muscular Dystrophy 2A
  • Sáenz, Amets
  • Azpitarte, Margarita
  • Armañanzas Arnedillo, Ruben
  • Leturcq, France
  • Alzualde, Ainhoa
  • Inza Cano, Iñaki
  • García Bragado, Federico
  • Herran, Gaspar de la
  • Corcuera, Julian
  • Cabello, Ana
  • Navarro, Carmen
  • Torre, Carolina de la
  • Gallardo, Eduard
  • Illa, Isabel
  • López de Munain, Adolfo
Item Type: Article
Título de Revista/Publicación: Plos One
Date: 2008
ISSN: 1932-6203
Volume: 3
Faculty: Facultad de Informática (UPM)
Department: Otro
Creative Commons Licenses: Recognition - No derivative works - Non commercial

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Limb-girdle muscular dystrophy type 2A (LGMD2A) is a recessive genetic disorder caused by mutations in calpain 3 (CAPN3). Calpain 3 plays different roles in muscular cells, but little is known about its functions or in vivo substrates. The aim of this study was to identify the genes showing an altered expression in LGMD2A patients and the possible pathways they are implicated in. Ten muscle samples from LGMD2A patients with in which molecular diagnosis was ascertained were investigated using array technology to analyze gene expression profiling as compared to ten normal muscle samples. Upregulated genes were mostly those related to extracellular matrix (different collagens), cell adhesion (fibronectin), muscle development (myosins and melusin) and signal transduction. It is therefore suggested that different proteins located or participating in the costameric region are implicated in processes regulated by calpain 3 during skeletal muscle development. Genes participating in the ubiquitin proteasome degradation pathway were found to be deregulated in LGMD2A patients, suggesting that regulation of this pathway may be under the control of calpain 3 activity. As frizzled-related protein (FRZB) is upregulated in LGMD2A muscle samples, it could be hypothesized that β-catenin regulation is also altered at the Wnt signaling pathway, leading to an incorrect myogenesis. Conversely, expression of most transcription factor genes was downregulated (MYC, FOS and EGR1). Finally, the upregulation of IL-32 and immunoglobulin genes may induce the eosinophil chemoattraction explaining the inflammatory findings observed in presymptomatic stages. The obtained results try to shed some light on identification of novel therapeutic targets for limb-girdle muscular dystrophies

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Item ID: 13980
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OAI Identifier:
DOI: 10.1371/journal.pone.0003750
Official URL:
Deposited by: Memoria Investigacion
Deposited on: 21 Dec 2012 10:30
Last Modified: 21 Apr 2016 13:26
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