Regulation of mRNA levels for pulmonary surfactant-associated proteins in developing rabbit lung.
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.
MRC Group in Fetal and Neonatal Health and Development, University of Western Ontario, London, Canada.
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J
Xu
L J
LJ
Yao
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F
Possmayer
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D005314:Embryonic and Fetal Development; D005325:Fetal Organ Maturity; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000235:genetics*; D008168:Lung / Q000196:embryology* / Q000378:metabolism; D011510:Proteolipids / Q000235:genetics*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D011817:Rabbits; D014158:Transcription, Genetic
D006023:Glycoproteins; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D003907:Dexamethasone