title: Changes in surfactant protein gene expression in a neonatal rabbit model of hyperoxia-induced fibrosis.
abstract: Lung injuries, including bronchopulmonary dysplasia, alter the surfactant system. We developed a newborn rabbit model of acute, followed by chronic, hyperoxic injury to study surfactant protein (SP) gene expression. Initial litters were exposed to >95% O2 until 50% died (LD50; 7-11 days old). Subsequent litters were exposed to >95% O2 for 8 days, followed by 60% O2 until 22-36 days. Controls were exposed to room air. LD50 animals displayed acute pulmonary inflammation, edema, protein leak, and surfactant dysfunction. These changes resolved, and fibrosis developed by 22 days. Whole lung SP-A mRNA expression (measured by membrane hybridization) was twice control levels at 4 days of >95% O2, with specific elevations in terminal bronchioles and type II cells at 4 days and the LD50 by in situ hybridization. Whole lung SP-B and SP-C mRNA were unchanged from control throughout exposure. However, in situ hybridization showed elevations in SP-B and SP-C mRNA in type II cells in inflamed areas at the LD50. SP mRNA alterations resolved by 22-36 days. The surfactant system recovers from acute hyperoxic injury, despite continued 60% O2 exposure.
authors.affiliation: Department of Pediatrics (Neonatology), Strong Children's Research Center, University of Rochester, New York 14642, USA.
authors.forename: C T
authors.initials: CT
authors.lastname: D'Angio
authors.forename: J N
authors.initials: JN
authors.lastname: Finkelstein
authors.forename: M B
authors.initials: MB
authors.lastname: Lomonaco
authors.forename: A
authors.initials: A
authors.lastname: Paxhia
authors.forename: S A
authors.initials: SA
authors.lastname: Wright
authors.forename: R B
authors.initials: RB
authors.lastname: Baggs
authors.forename: R H
authors.initials: RH
authors.lastname: Notter
authors.forename: R M
authors.initials: RM
authors.lastname: Ryan
mesh_terms: D000208:Acute Disease; D000818:Animals; D000831:Animals, Newborn; D002908:Chronic Disease; D015870:Gene Expression; D018496:Hyperoxia / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D017403:In Situ Hybridization; D011658:Pulmonary Fibrosis / Q000209:etiology* / Q000235:genetics*; D011663:Pulmonary Surfactants / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits
chemical_list: D011663:Pulmonary Surfactants; D012333:RNA, Messenger