RT Journal Article
SR Electronic
T1 Atrophy and hypertrophy signalling in the diaphragm of patients with COPD
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 549
OP 556
DO 10.1183/09031936.00091108
VO 35
IS 3
A1 Testelmans, D.
A1 Crul, T.
A1 Maes, K.
A1 Agten, A.
A1 Crombach, M.
A1 Decramer, M.
A1 Gayan-Ramirez, G.
YR 2010
UL http://erj.ersjournals.com/content/35/3/549.abstract
AB We investigated whether atrophy and hypertrophy signalling were altered in the diaphragm of chronic obstructive pulmonary disease (COPD) patients. We studied diaphragm fibre dimensions and proportion, expression of markers of the ubiquitin-proteasome pathway, nuclear factor (NF)-κB pathways, muscle regulatory factors and myostatin in diaphragm biopsies from 19 patients with severe COPD and 13 patients without COPD. Type I proportion was significantly increased in the diaphragm of COPD patients while type II proportion was decreased. The cross-sectional area of all fibre types was reduced in the COPD patients. In addition, MAFbx mRNA was higher in the diaphragm of COPD patients while Nedd4 mRNA decreased. Cytoplasmatic levels of inhibitor protein IκBα and IκBβ were decreased in the COPD patients as was NF-κB p50 DNA-binding activity. MyoD mRNA and its nuclear protein content were decreased in the diaphragm of COPD patients and myogenin mRNA and protein levels remained unchanged. Myostatin mRNA was decreased but its protein levels in the nuclear and cytoplasmic fraction were significantly increased in the COPD patients. These data show that the ubiquitin-proteasome pathway, the NF-κB pathway and myostatin protein were up-regulated in the diaphragm of COPD patients while MyoD expression was reduced. These alterations may contribute to diaphragm remodeling in COPD.