title: [Reduction of muscle mass mediated by myostatin in an experimental model of pulmonary emphysema].
abstract: BACKGROUND
  Among the extrapulmonary manifestations of COPD, dysfunction and loss of muscle mass/weight are those that have the greatest impact on the quality of life of patients. Our objective was to evaluate the molecular mechanisms that are potentially implicated in the limited development of muscle mass in the diaphragm and gastrocnemius of mice with experimentally-induced emphysema.
  
  
  METHODS
  An experimental model in mice, in which emphysema was induced by means of the local instillation of elastase (n=6), while saline was administered to the controls (n=7). We determined the levels of oxidative stress, proteolytic systems, signaling pathways, growth factors and cell differentiation (western-blot) in the diaphragm and gastrocnemius of all the mice after 34 weeks.
  
  
  RESULTS
  Upon comparing the mice with emphysema with the controls, the following findings were observed: (1) lower total body weight and lower weight of the diaphragm and gastrocnemius; (2) in the diaphragm, the levels of protein oxidation were increased, the mitochondrial antioxidant systems reduced, the levels of myostatin and of the ERK1/2 and FoxO1 signaling pathways were higher, and the myosin content was lower (67%); and (3) in the gastrocnemius of the emphysematous mice, the cytosolic antioxidants were decreased and the levels of myostatin and of the JNK and NF-kB signaling pathways were increased.
  
  
  CONCLUSIONS
  The reduction of the myosin content observed in the diaphragm of mice with emphysema could explain their smaller size. Oxidative stress, myostatin and FoxO could be implicated in the loss of this structural protein.
authors: Servicio de Neumología-Grupo de Mecanismos Moleculares de Predisposición al Cáncer de Pulmón (MMPCP), Instituto Municipal de Investigación Médica (IMIM)-Hospital del Mar, Parc de Salut Mar, Departamento de Ciencias Experimentales y de la Salud, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona (PRBB), España.
authors: Clara
authors: C
authors: Fermoselle
authors: Francisco
authors: F
authors: Sanchez
authors: Esther
authors: E
authors: Barreiro
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000032:analysis; D003600:Cytosol / Q000737:chemistry; D003964:Diaphragm / Q000737:chemistry / Q000473:pathology; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000502:physiology; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D009133:Muscular Atrophy / Q000209:etiology* / Q000378:metabolism; D009218:Myosins / Q000172:deficiency*; D055435:Myostatin / Q000032:analysis / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D009929:Organ Size; D018384:Oxidative Stress; D010196:Pancreatic Elastase / Q000633:toxicity; D059748:Proteolysis; D011656:Pulmonary Emphysema / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D012132:Respiratory Muscles / Q000378:metabolism / Q000473:pathology*; D015431:Weight Loss
chemical_list: D000975:Antioxidants; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; C525912:Mstn protein, mouse; D055435:Myostatin; D016328:NF-kappa B; D010196:Pancreatic Elastase; D009218:Myosins