Increased type I procollagen mRNA in airways and pulmonary vessels after vagal denervation in rats.
To test the hypothesis that increased airway strain resulting from lung denervation initiates a fibroproliferative response in the airways, we compared the transcriptional expressions of alpha1(I)-procollagen and tropoelastin in the lungs of rats subjected to unilateral vagal denervation, unilateral vagal denervation combined with ipsilateral phrenectomy, or thoracotomy without denervation (controls). We found increases in alpha1(I)-procollagen messenger ribonucleic acids (mRNAs) in the submucosa of the airways and the adventitia of airways and pulmonary vessels of the denervated lungs in 31% of the rats subjected to unilateral denervation (with and without phrenectomy), and in none of the controls. The increased transcripts were associated with collagen deposition in the peribronchial and perivascular tissue, and occasionally with cell proliferation leading to occlusion of the airway and vascular lumina. Unilateral phrenectomy did not decrease the frequency with which production of Type I procollagen was upregulated, suggesting that the upregulation was not entirely dependent on airway strain. Tropoelastin expression was not influenced by denervation. Our results indicate that the autonomic nervous system has a previously unsuspected trophic influence on collagen synthesis in the airways and pulmonary vessels. Abolition of this influence by denervation may lead to structural changes analogous to those observed in bronchiolitis obliterans after lung transplantation.
Carver
T W
TW
The Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Srinathan
S K
SK
Velloff
C R
CR
Pérez Fontán
J J
JJ
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D003714:Denervation; D017403:In Situ Hybridization; D008168:Lung / Q000098:blood supply*; D008297:Male; D011347:Procollagen / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea / Q000378:metabolism*; D014333:Tropoelastin / Q000235:genetics; D014628:Vagotomy
D011347:Procollagen; D012333:RNA, Messenger; D014333:Tropoelastin