Alterations in gene expression in hamster diaphragm after emphysema and lung volume reduction surgery.
The authors have demonstrated previously that emphysema and lung volume reduction surgery (LVRS) resulted in a significant shift of type IIx/b to type IIa fibres in the diaphragm of hamsters with elastase-induced emphysema. To explore the mechanisms leading to this fibre switching, the mRNA expression of the myogenic regulatory factors, the inhibitors of DNA binding proteins (Id-proteins) and insulin-like growth factor-I were examined. Ribonucleic acid was extracted from the diaphragm of control, emphysematous, emphysematous and sham operated and LVRS hamsters and subjected to reverse transcriptase polymerase chain reaction. Compared to control, the ratio MyoD to myogenin declined with emphysema, sham and even more after LVRS, due to a decrease in MyoD mRNA and an increase in myogenin mRNA. Similarly, compared to control, Id-1 protein mRNA levels decreased significantly in sham and even more in LVRS. Id-2 protein mRNA levels decreased in all groups, but reached statistical significance in LVRS only, compared to control.


CONCLUSIONS
1) the reduced MyoD/myogenin ratio may be the mechanism of the shift to a slower fibre type, 2) the decreased MyoD/myogenin ratio in lung volume reduction surgery animals suggests that lung volume reduction surgery enhances rather than decreases the load placed on the diaphragm and 3) the observed down-regulation of the inhibiting factors may facilitate the diaphragm adaptation to overload.
Reynders
V
V
Respiratory Muscle Research Unit, University Hospitals, Katholieke Universiteit Leuven, Belgium.
Marchand
E
E
Gayan-Ramirez
G
G
De Leyn
P
P
Verhoeven
G
G
Decramer
M
M
D000818:Animals; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000235:genetics; D003964:Diaphragm / Q000473:pathology / Q000502:physiology*; D004195:Disease Models, Animal; D004646:Emphysema / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery*; D005652:Functional Residual Capacity; D015870:Gene Expression / Q000502:physiology; D051798:Inhibitor of Differentiation Protein 1; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008297:Male; D008647:Mesocricetus; D009124:Muscle Proteins / Q000235:genetics; D017570:MyoD Protein / Q000235:genetics; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D009929:Organ Size; D011013:Pneumonectomy; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics
D004268:DNA-Binding Proteins; C490128:ID4 protein, human; D051798:Inhibitor of Differentiation Protein 1; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; D009124:Muscle Proteins; D017570:MyoD Protein; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C075640:ID3 protein, human; D007334:Insulin-Like Growth Factor I