TRANSFORMING GROWTH FACTOR ALPHA (TGF ) IS INCREASED DURING HYPEROXIA AND FIBROSIS

• Published in: Experimental lung research 2002, Vol.28 (5), p.361-372
• Main Authors: Waheed, Saira, D'Angio, Carl T., Wagner, Carol L., Madtes, David K., Finkelstein, Jacob N., Paxhia, Anna, Ryan, Rita M.
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Alveolar Epithelial Repair; Animals; Animals, Newborn; Biological and medical sciences; Bronchoalveolar Lavage Fluid; Cell Division - drug effects; Fibroblast Growth Factor 7; Fibroblast Growth Factors - pharmacology; Fibrosis Lung; Hyperoxia - metabolism; Hyperoxia - pathology; Injury; Medical sciences; Mice; Mice, Knockout; Pneumology; Pulmonary Alveoli - metabolism; Pulmonary Alveoli - pathology; Pulmonary Fibrosis - metabolism; Pulmonary Fibrosis - pathology; Rabbits; Respiratory Mucosa - metabolism; Respiratory Mucosa - pathology; Respiratory system : syndromes and miscellaneous diseases; Sodium Chloride - pharmacology; Transforming Growth Factor alpha - genetics; Transforming Growth Factor alpha - metabolism
• ISSN: 0190-2148; 1521-0499
• DOI: 10.1080/01902140290091994

Transforming growth factor alpha (TGF α) stimulates type II alveolar epithelial cell proliferation and also is associated with fibrosis. We studied the changes in bronchoalveolar lavage (BAL) TGF α protein in a neonatal rabbit hyperoxia-fibrosis model (100% O 2 for 8 to 9 days, followed by 60% O 2 to 36 days of age). Hyperoxia increased TGF α protein and delayed the appearance of mature lower molecular weight (MW) TGF α isoforms at postnatal days 6 and 8 during the acute injury period. At 3 and 5 weeks, after chronic hyperoxia exposure, there was an increase in lower MW TGF α peptides during the fibrotic period. Keratinocyte growth factor (KGF) is also a type II cell mitogen. In vitro studies of keratinocytes suggest that KGF-induced proliferation is mediated through TGF α. Intratracheal KGF instillation into adult wild-type and TGF α -null mice demonstrated that the KGF induced equivalent robust levels of proliferation in both TGF α deficient and wild-genotype mice. In conclusion, there are both quantitative and qualitative changes in TGF α protein in a hyperoxia-induced fibrosis neonatal rabbit model during periods of type II cell proliferation and fibrosis.