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

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Abstract
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.

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