Abstract
Expression of the surfactant protein A (SP-A) gene is lung specific, developmentally induced, and regulated by adenosine 3',5'-cyclic monophosphate (cAMP) and glucocorticoids. Humans have two highly similar genes encoding SP-A (SP-A1 and SP-A2). In the companion paper [S.M. McCormick, V. Boggaram, and C.R. Mendelson Am. J. Physiol. 266 (Lung Cell. Mol. Physiol. 10): L354-L366, 1994] we report that SP-A1 and SP-A2 RNA transcripts are alternatively spliced at their 5' ends, resulting in nine different primer-extended transcripts. In the present study, primer extension was used to assess the relative levels of expression of the SP-A1 and SP-A2 genes in human adult lung tissue and in fetal lung tissues maintained in organ culture in the absence or presence of dibutyryl (DB)cAMP (1 mM) and dexamethasone (Dex, 10-7 M). Primer extension and Northern analysis were used to assess the effects of these agents on the levels of expression of these genes. In human adult lung tissue, 65% of the SP-A mRNA transcripts were derived from the SP-A2 gene, whereas only 35% were from SP-A1. On the other hand, in lung tissue from a 28-wk gestation neonate, only SP-A1 mRNA transcripts were detected, and, in midgestation fetal lung cultured in control medium, 65% of the SP-A mRNA was found to be SP-A1 and 35% was SP- A2. By contrast, when lung explants were incubated in the presence of DBcAMP, 67% of the SP-A mRNA transcripts were derived from the SP-A2 gene, and the remaining 33% were from SP-A1. In lung tissues treated with DBcAMP plus Dex, the ratio of SP-A2 to SP-A1 was shifted to a value similar to that observed in control tissues. Interestingly, DBcAMP caused an 11-fold increase in SP- A2 mRNA levels, whereas only a 2-fold induction by cAMP of SP-A1 mRNA levels was observed. Dex had little or no effect in reducing the levels of SP-A1 mRNA in DBcAMP-treated human fetal lung explants but caused a 90% reduction in the levels of SP-A2 mRNA. These findings suggest that the human SP-A2 gene is more responsive to the inductive effects of cAMP and the inhibitory effects of glucocorticoids than that encoding SP-A1.
Original language | English (US) |
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Pages (from-to) | L367-L374 |
Journal | American Journal of Physiology - Lung Cellular and Molecular Physiology |
Volume | 266 |
Issue number | 4 10-4 |
DOIs | |
State | Published - 1994 |
Keywords
- Northern analysis
- adult lung
- dexamethasone
- dibutyryl adenosine 3',5'-cyclic monophosphate
- fetal lung
- messenger ribonucleic acid
- primer extension
- surfactant protein A
ASJC Scopus subject areas
- Physiology
- Pulmonary and Respiratory Medicine
- Physiology (medical)
- Cell Biology