Developmental and hormonal regulation of surfactant protein C (SP-C) gene expression in fetal lung. Role of transcription and mRNA stability.
Pulmonary surfactant protein C (SP-C) gene expression is developmentally and hormonally regulated in fetal lung. In the present study, we investigated the role of transcriptional and posttranscriptional mechanisms in the developmental, cAMP, and dexamethasone induction of SP-C mRNA. We found that developmental induction of SP-C mRNA was not coincident with induction of SP-C gene transcription. SP-C mRNA levels reached approximately 90% of levels in adult lung on day 24 of gestation, whereas SP-C gene transcription was only approximately 4% of level in adult lung and did not increase until day 28 of gestation (term in rabbit = 31 days). Treatment of fetal lung tissues in vitro with dibutyryl cyclic AMP (Bt2cAMP) and dexamethasone increased SP-C mRNA accumulation by different mechanisms. Increase in SP-C mRNA accumulation by Bt2cAMP was the result of increased SP-C gene transcription, whereas increased SP-C mRNA accumulation by dexamethasone was due to stabilization of RNA. In control tissues the SP-C mRNA half-life (t1/2) was 11.2 h, and after dexamethasone treatment it increased to 30 h. These data show that both transcriptional and mRNA stabilization mechanisms regulate induction of SP-C gene expression during fetal lung development and by cAMP and dexamethasone in fetal lung in vitro.
Department of Molecular Biology, University of Texas Health Science Center, Tyler 75710.
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Boggaram
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Margana
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008168:Lung / Q000196:embryology; D009924:Organ Culture Techniques; D011510:Proteolipids / Q000235:genetics*; D011663:Pulmonary Surfactants / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D014158:Transcription, Genetic / Q000187:drug effects
D011510:Proteolipids; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D003994:Bucladesine; D003907:Dexamethasone