Document Detail

Glucocorticoid regulation of human pulmonary surfactant protein-B mRNA stability involves the 3'-untranslated region.
MedLine Citation:
PMID:  18006875     Owner:  NLM     Status:  MEDLINE    
Expression of pulmonary surfactant, a complex mixture of lipids and proteins that acts to reduce alveolar surface tension, is developmentally regulated and restricted to lung alveolar type II cells. The hydrophobic protein surfactant protein-B (SP-B) is essential in surfactant function, and insufficient levels of SP-B result in severe respiratory dysfunction. Glucocorticoids accelerate fetal lung maturity and surfactant synthesis both experimentally and clinically. Glucocorticoids act transcriptionally and post-transcriptionally to increase steady-state levels of human SP-B mRNA; however, the mechanism(s) by which glucocorticoids act post-transcriptionally is unknown. We hypothesized that glucocorticoids act post-transcriptionally to increase SP-B mRNA stability via sequence-specific mRNA-protein interactions. We found that glucocorticoids increase SP-B mRNA stability in isolated human type II cells and in nonpulmonary cells, but do not alter mouse SP-B mRNA stability in a mouse type II cell line. Deletion analysis of an artificially-expressed SP-B mRNA indicates that the SP-B mRNA 3'-untranslated region (UTR) is necessary for stabilization, and the region involved can be restricted to a 126-nucleotide-long region near the SP-B coding sequence. RNA electrophoretic mobility shift assays indicate that cytosolic proteins bind to this region in the absence or presence of glucocorticoids. The formation of mRNA:protein complexes is not seen in other regions of the SP-B mRNA 3'-UTR. These results indicate that a specific 126-nucleotide region of human SP-B 3'-UTR is necessary for increased SP-B mRNA stability by glucocorticoids by a mechanism that is not lung cell specific and may involve mRNA-protein interactions.
Helen W Huang; Weizhen Bi; Gaye N Jenkins; Joseph L Alcorn
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-11-15
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  38     ISSN:  1535-4989     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-03-19     Completed Date:  2008-04-01     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  473-82     Citation Subset:  IM    
Department of Pediatrics, University of Texas-Houston Medical School, 6431 Fannin, suite 3.222, Houston, TX 77030, USA.
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MeSH Terms
3' Untranslated Regions / genetics*
Base Pairing / drug effects
Base Sequence
Binding, Competitive / drug effects
Cell Separation
Cells, Cultured
Cytosol / drug effects,  metabolism
Dactinomycin / pharmacology
Dexamethasone / pharmacology*
Electrophoretic Mobility Shift Assay
Gene Expression Regulation / drug effects
Glucocorticoids / pharmacology*
Protein Binding / drug effects
Pulmonary Alveoli / cytology,  drug effects,  metabolism
Pulmonary Surfactant-Associated Protein B / genetics*,  metabolism
RNA Stability / drug effects*
Grant Support
Reg. No./Substance:
0/3' Untranslated Regions; 0/Glucocorticoids; 0/Pulmonary Surfactant-Associated Protein B; 50-02-2/Dexamethasone; 50-76-0/Dactinomycin

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