Transcriptional regulation of the gene encoding the major surfactant protein (SP-A) in rabbit fetal lung

Abstract

The expression of the major protein of rabbit pulmonary surfactant (SP-A), a glycoprotein of Mr congruent to 29,000-36,000, is regulated during development and by hormones. In the present study, utilizing a cDNA insert complementary to mRNA coding for SP-A and nuclear transcription elongation assays, we have investigated the developmental and hormonal regulation of transcription of the SP-A gene in rabbit fetal lung tissue. The relative rates of transcription of SP-A mRNA increased as a function of the gestational age of the fetus. The rate of transcription reached a maximum level in lung tissues of 28-day gestational age fetuses and declined slightly in those of neonatal rabbits. The relative rate of transcription of SP-A mRNA increased in rabbit fetal lung explants maintained in organ culture in control medium as a function of incubation time. Dibutyryl cyclic AMP (Bt2cAMP) treatment of fetal lung explants increased the rate of transcription of SP-A mRNA over that of control tissues by several-fold; after 12 h of incubation in the presence of Bt2cAMP, there was greater than 4-fold increase in the rate of transcription of SP-A mRNA as compared to control lung explants. In contrast, glucocorticoids had a rapid effect to decrease the rate of SP-A mRNA transcription. The rapid effect of glucocorticoids to inhibit the transcription of SP-A mRNA was transient; in fetal lung explants incubated in the presence of dexamethasone for greater than 24 h, there was an increase in the rate of transcription of SP-A mRNA over that of control explants. Cycloheximide caused an inhibition of both basal as well as Bt2cAMP-stimulated rates of transcription of SP-A mRNA in the rabbit fetal lung tissue in vitro. This finding is suggestive of a role of labile protein factor(s) in mediating transcription of the SP-A gene as well as its induction by Bt2cAMP. The magnitude of changes in the relative rates of transcription of SP-A mRNA during development of rabbit fetal lung in vitro as well as those effected by hormones in vitro were similar to changes in the steady-state levels of SP-A mRNA, suggestive that the regulation of the levels of SP-A mRNA in fetal rabbit lung tissue both in vivo and in vitro occurs primarily at the transcriptional level.