European Respiratory Journal vol:35 issue:3 pages:549-556
We investigated whether atrophy and hypertrophy signaling was altered in the diaphragm of COPD patients.Diaphragm fiber dimensions and proportion, expression of markers of the ubiquitin-proteasome, the NF-kappaB pathways, the muscle regulatory factors and myostatin were studied 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. Cross-sectional area of all fiber 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 IkappaBalpha and IkappaBbeta were decreased in the COPD patients as was the nuclear NF-kappaB 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 showed that the ubiquitin-proteasome pathway, the NF-kappaB pathway and myostatin protein were upregulated in the diaphragm of COPD patients while MyoD expression was reduced. These alterations may contribute to diaphragm remodeling in COPD.