title: O2 regulates surfactant protein A mRNA transcription and stability in human fetal lung in vitro.
abstract: The effect of O2 on surfactant protein (SP) A mRNA transcription and half-life was determined in midtrimester human fetal lung tissue cultured in either 20 (control) or 70% O2. Incubation of tissues in 70% O2 resulted in a 133% increase in SP-A mRNA transcription rate compared with control tissues. The SP-A mRNA half-life was increased by 54% in lung tissues cultured in 70% O2 vs. control tissues. Western blot analysis indicated a threefold increase in SP-A in the 70% O2 condition, demonstrating that O2 regulation of SP-A mRNA levels results in corresponding changes in SP-A levels. Primer extension assays were performed to determine whether the observed increase in SP-A mRNA levels is secondary to the preferential expression of one of the human SP-A genes, SP-A1 or SP-A2. Transcripts of both the SP-A1 and SP-A2 genes were increased approximately 100% in tissues maintained in 70% O2 compared with control tissues. These data demonstrate that O2 regulates human SP-A mRNA levels by both transcriptional and posttranscriptional mechanisms. Furthermore, because there is no differential effect of O2 on the expression of SP-A1 vs. SP-A2 mRNA, the properties of these genes that mediate regulation by O2 must be conserved between the two genes.
authors.affiliation: Department of Pediatrics, University of Iowa College of Medicine, Iowa City 52242, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Acarregui
authors.forename: A R
authors.initials: AR
authors.lastname: Kumar
authors.forename: S T
authors.initials: ST
authors.lastname: Penisten
authors.forename: J M
authors.initials: JM
authors.lastname: Snyder
mesh_terms: D006801:Humans; D008168:Lung / Q000196:embryology*; D009924:Organ Culture Techniques; D010100:Oxygen / Q000378:metabolism*; D011510:Proteolipids / Q000235:genetics* / Q000378:metabolism; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; C445842:SFTPA1 protein, human; C445843:SFTPA2 protein, human; D010100:Oxygen