Article Text

Atrophy and hypertrophy signalling of the quadriceps and diaphragm in COPD
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  1. Mariève Doucet1,
  2. Annie Dubé1,
  3. Denis R Joanisse1,2,
  4. Richard Debigaré1,
  5. Annie Michaud1,
  6. Marie-Ève Paré1,
  7. Rosaire Vaillancourt1,
  8. Éric Fréchette1,
  9. François Maltais1
  1. 1Centre de recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Canada
  2. 2Division de Kinésiologie, Université Laval, Québec, Canada
  1. Correspondence to Dr François Maltais, Centre de Pneumologie, Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Chemin Ste-Foy, Québec, QC, G1V 4G5, Canada; francois.maltais{at}med.ulaval.ca

Abstract

Background Factors involved in the regulation of muscle mass in chronic obstructive pulmonary disease (COPD) are still poorly understood. Comparing the signalisation involved in muscle mass regulation between two muscles with different levels of activation within the same subjects is an interesting strategy to tease out the impact of local (muscle activity) versus systemic factors in the regulation of muscle mass. A study was undertaken to measure and compare the protein levels of p-AKT, AKT, Atrogin-1, p-p70S6K, p-4E-BP1, p-GSK3β as well as the mRNA expression of Atrogin-1, MuRF1 and FoxO-1 in the quadriceps and the diaphragm of 12 patients with COPD and 7 controls with normal lung function.

Methods Diaphragm biopsies were obtained during thoracic surgery and quadriceps samples were obtained from needle biopsies. Protein content and mRNA expression were measured by western blot and quantitative PCR, respectively.

Results Increased mRNA expressions of Atrogin-1, MuRF1 and FoxO-1 were found in the quadriceps compared with the diaphragm only in patients with COPD. The quadriceps/diaphragm ratio for MuRF1 was higher in COPD. The protein level of p-p70S6K was decreased in the quadriceps compared with the diaphragm in patients with COPD. The quadriceps/diaphragm ratios of p-p70S6K and p-GSK3β were lower in patients with COPD than in controls.

Conclusions These results indicate a greater susceptibility to a catabolic/anabolic imbalance favouring muscle atrophy in the quadriceps compared with the diaphragm in patients with COPD. The balance between the atrophy and hypertrophy signalling is inhomogeneous between respiratory and lower limb muscles, suggesting that local factors are likely to be involved in the regulation of muscle mass in COPD.

  • Chronic obstructive pulmonary disease
  • muscle
  • atrophy
  • wasting
  • cachexia
  • inactivity
  • p70S6K
  • E3-ligases
  • FoxO-1
  • COPD mechanisms
  • respiratory muscles
  • systemic disease and lungs

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  • Web Only Data THORAX.2009.133827

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Footnotes

  • Funding Canadien Institutes of Health Research grant MOP-84091. FM holds a GSK/CIHR Research Chair on COPD at Université Laval.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Comité d'Éthique de la Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec and each patient signed a written informed consent form.

  • Provenance and peer review Not commissioned; externally peer reviewed.