title: Transforming growth factor alpha (TGF(alpha)) is increased during hyperoxia and fibrosis.
abstract: Transforming growth factor alpha (TGF(alpha)) stimulates type II alveolar epithelial cell proliferation and also is associated with fibrosis. We studied the changes in bronchoalveolar lavage (BAL) TGF(alpha) 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(alpha) protein and delayed the appearance of mature lower molecular weight (MW) TGF(alpha) 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(alpha) 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(alpha). Intratracheal KGF instillation into adult wild-type and TGF(alpha)-null mice demonstrated that the KGF induced equivalent robust levels of proliferation in both TGF(alpha) deficient and wild-genotype mice. In conclusion, there are both quantitative and qualitative changes in TGF(alpha) protein in a hyperoxia-induced fibrosis neonatal rabbit model during periods of type II cell proliferation and fibrosis.
authors.affiliation: Department of Pediatrics (Neonatology), University of Rochester, Rochester, New York, USA.
authors.forename: Saira
authors.initials: S
authors.lastname: Waheed
authors.forename: Carl T
authors.initials: CT
authors.lastname: D'Angio
authors.forename: Carol L
authors.initials: CL
authors.lastname: Wagner
authors.forename: David K
authors.initials: DK
authors.lastname: Madtes
authors.forename: Jacob N
authors.initials: JN
authors.lastname: Finkelstein
authors.forename: Anna
authors.initials: A
authors.lastname: Paxhia
authors.forename: Rita M
authors.initials: RM
authors.lastname: Ryan
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D001992:Bronchoalveolar Lavage Fluid; D002455:Cell Division / Q000187:drug effects; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D018496:Hyperoxia / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology; D011817:Rabbits; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology; D012965:Sodium Chloride / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: C496454:Fgf7 protein, mouse; D016211:Transforming Growth Factor alpha; D051523:Fibroblast Growth Factor 7; D012965:Sodium Chloride; D005346:Fibroblast Growth Factors