O-2 REGULATES SURFACTANT PROTEIN-A MESSENGER-RNA TRANSCRIPTION AND STABILITY IN HUMAN FETAL LUNG IN-VITRO

The effect of O-2 On surfactant protein (SP) A mRNA transcription and half-life was determined in midtrimester human fetal lung tissue cultu red in either 20 (control) or 70% O-2. Incubation of tissues in 70% O- 2 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% O-2, vs. control tissues. Western blot a nalysis indicated a threefold increase in SP-A in the 70% O-2 conditio n, demonstrating that O-2 regulation of SP-A mRNA levels results in co rresponding changes in SP-A levels. Primer extension assays were perfo rmed to determine whether the observed increase in SP-A mRNA levels is secondary to the preferential expression of one of the human SP-A gen es, SP-A1 or SP-A2. Transcripts of both the SP-A1 and SP-A2 genes were increased similar to 100% in tissues maintained in 70% Og compared wi th control tissues. These data demonstrate that O-2 regulates human SP -A mRNA levels by both transcriptional and posttranscriptional mechani sms. Furthermore, because there is no differential effect of O-2 on th e expression of SP-A1 vs. SP-A2 mRNA, the properties of these genes th at mediate regulation by O-2 must be conserved between the two genes.