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Regulation of mRNA levels for pulmonary surfactant-associated proteins in developing rabbit lung
1MRC Group in Fetal and Neonatal Health and Development, University of Western Ontario, London, Canada.
Abstract:
Gene transcriptional activities and steady-state mRNA levels have been examined for the surfactant-associated proteins SP-A, SP-B and SP-C in developing rabbit lung. It was observed SP-C mRNA levels increase early in gestation, while SP-A and SP-B mRNA levels increase rapidly between 26 and 30 days gestation. Transcriptional activities for all three surfactant apoproteins increase between 26 and 30 days. Studies conducted with fetal lung explants of 26 days gestation demonstrated exposure to low doses of dexamethasone increases SP-A and SP-C mRNA levels, while high doses stimulate transcription, although this only significant for SP-C. Time course studies revealed different temporal patterns and glucocorticoid responses for SP-A and SP-C mRNAs. SP-A and SP-C mRNA production and steady-state levels were reduced after treatment with cycloheximide. In contrast, SP-B gene transcription was selectively stimulated, suggesting involvement of a labile negative regulatory factory. It is concluded that expression of the three surfactant apoproteins is independently regulated. Early in gestation, SP-C mRNA levels may be regulated in vivo through message stabilization. Glucocorticoids can affect SP-A and SP-C mRNA levels in culture at both transcriptional and post-transcriptional levels. The ability of glucocorticoids to influence these processes declines during fetal development.
Insights
Gene expression for surfactant proteins SP-A, SP-B, and SP-C in developing rabbit lungs is independently regulated. Glucocorticoids influence these surfactant apoprotein mRNA levels during fetal development.
Area of Science:
- Pulmonary Medicine
- Developmental Biology
- Molecular Genetics
Background:
- Surfactant-associated proteins (SP-A, SP-B, SP-C) are crucial for lung function.
- Understanding the regulation of surfactant protein gene expression during lung development is essential.
Purpose of the Study:
- To investigate the regulation of SP-A, SP-B, and SP-C gene expression and mRNA levels in developing rabbit lungs.
- To examine the effects of dexamethasone and cycloheximide on surfactant apoprotein gene expression.
Main Methods:
- Analysis of gene transcriptional activities and steady-state mRNA levels.
- Studies using fetal lung explants treated with dexamethasone and cycloheximide.
- Time course studies to observe temporal patterns and responses.
Main Results:
- SP-C mRNA levels increase early in gestation; SP-A and SP-B mRNA levels increase rapidly between 26-30 days gestation.
- Transcriptional activities for all three proteins increase between 26-30 days gestation.
- Dexamethasone affects SP-A and SP-C mRNA levels transcriptionally and post-transcriptionally, with effects diminishing during development. Cycloheximide reduces SP-A and SP-C mRNA, while stimulating SP-B transcription.
Conclusions:
- Expression of SP-A, SP-B, and SP-C is independently regulated.
- SP-C mRNA regulation may involve message stabilization early in gestation.
- Glucocorticoid influence on surfactant apoprotein gene expression changes during fetal development.