Transcriptional Regulation of the Surfactant Protein-A Gene in Fetal Lung

CHEST Journal ◽  
1997 ◽  
Vol 111 (6) ◽  
pp. 96S-104S ◽  
Author(s):  
Carole R. Mendelson ◽  
Erwei Gao ◽  
Pampee P. Young ◽  
Laura F. Michael ◽  
Joseph L. Alcorn
Keyword(s):  
Transcriptional Regulation ◽  
Protein A ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Surfactant Protein A

Antisense inhibition of surfactant protein A decreases tubular myelin formation in human fetal lung in vitro

2002 ◽  
Vol 282 (3) ◽  
pp. L386-L393 ◽  
Author(s):  
Jonathan M. Klein ◽  
Troy A. McCarthy ◽  
John M. Dagle ◽  
Jeanne M. Snyder
Keyword(s):  
Gene Expression ◽  
Protein A ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Mrna Levels ◽  
Phosphorothioate Oligonucleotide ◽  
Myelin Formation ◽  
Surfactant Phospholipids ◽  
Human Fetal Lung

Surfactant protein A (SP-A) is the most abundant of the surfactant-associated proteins. SP-A is involved in the formation of tubular myelin, the modulation of the surface tension-reducing properties of surfactant phospholipids, the metabolism of surfactant phospholipids, and local pulmonary host defense. We hypothesized that elimination of SP-A would alter the regulation of SP-B gene expression and the formation of tubular myelin. Midtrimester human fetal lung explants were cultured for 3–5 days in the presence or absence of an antisense 18-mer phosphorothioate oligonucleotide (ON) complementary to SP-A mRNA. After 3 days in culture, SP-A mRNA was undetectable in antisense ON-treated explants. After 5 days in culture, levels of SP-A protein were also decreased by antisense treatment. SP-B mRNA levels were not affected by the antisense SP-A ON treatment. However, there was decreased tubular myelin formation in the antisense SP-A ON-treated tissue. We conclude that selective elimination of SP-A mRNA and protein results in a decrease in tubular myelin formation in human fetal lung without affecting SP-B mRNA. We speculate that SP-A is critical to the formation of tubular myelin during human lung development and that the regulation of SP-B gene expression is independent of SP-A gene expression.

scholarly journals Transcriptional Regulation of the Murine Surfactant Protein-A Gene by B-Myb

1999 ◽  
Vol 274 (39) ◽  
pp. 27523-27528 ◽  
Author(s):  
Michael D. Bruno ◽  
Jeffrey A. Whitsett ◽  
Gary F. Ross ◽  
Thomas R. Korfhagen
Keyword(s):  
Transcriptional Regulation ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A

Surfactant protein A expression is delayed in fetuses of streptozotocin-treated rats

1992 ◽  
Vol 262 (4) ◽  
pp. L489-L494 ◽  
Author(s):  
S. H. Guttentag ◽  
D. S. Phelps ◽  
W. Stenzel ◽  
J. B. Warshaw ◽  
J. Floros
Keyword(s):  
Protein A ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Female Rats ◽  
Surfactant Protein A ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Normal Expression

The content and distribution of the 26-to 38-kDa surfactant protein (SP-A) and its mRNA were determined in fetuses of control and streptozotocin (STZ)-treated Sprague-Dawley rats using immunohistochemistry, RNA blotting, and in situ hybridization. Female rats were treated with 50 mg/kg STZ before mating, and the fetuses were killed at fetal days 18-21 or on neonatal days 1 and 2 (day of birth = end of day 22). SP-A was barely detectable on fetal day 18 in controls and easily detected by fetal day 21. In the STZ group, SP-A was decreased compared with controls at fetal days 18-21. However, by neonatal days 1–2, there were no significant differences in SP-A levels between groups. SP-A mRNA was detectable at fetal day 18 in controls, but it was decreased in the STZ group at day 18-21 (P less than 0.02) and differences were no longer detected by neonatal days 1–2. SP-A and SP-A mRNA accumulated with advancing gestational age in both groups until neonatal days 1–2. The differences in SP-A and SP-A mRNA levels in the two groups diminished with advancing age but remained significant at fetal day 21. These data suggest that STZ-induced diabetes interferes with normal expression of SP-A in the developing fetal lung.

scholarly journals Genomic elements involved in transcriptional regulation of the rabbit surfactant protein-A gene.

1993 ◽  
Vol 7 (8) ◽  
pp. 1072-1085
Author(s):  
J L Alcorn ◽  
E Gao ◽  
Q Chen ◽  
M E Smith ◽  
R D Gerard ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A

Characterization of two baboon surfactant protein A genes

1996 ◽  
Vol 271 (4) ◽  
pp. L617-L630 ◽  
Author(s):  
E. Gao ◽  
Y. Wang ◽  
S. M. McCormick ◽  
J. Li ◽  
S. R. Seidner ◽  
...  
Keyword(s):  
Transcription Initiation ◽  
Protein A ◽  
Fetal Lung ◽  
Polymerase Chain Reaction Analysis ◽  
Single Copy ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Gene Encoding ◽  
Glucocorticoid Treatment ◽  
Rats And Mice

The gene encoding surfactant protein A (SP-A) is expressed in type II pneumonocytes and is developmentally and hormonally regulated in fetal lung tissue. SP-A is encoded by a single-copy gene in rabbits, dogs, rats, and mice. By contrast, the human genome contains two similar genes, hSP-A1 and hSP-A2, which are differentially regulated during development and differentially regulated by adenosine 3',5'-cyclic monophosphate (cAMP) and glucocorticoid treatment of human fetal lung in culture. In the present study, we have isolated and characterized baboon genomic clones containing two highly similar SP-A genes. Restriction mapping of these clones, together with Southern analysis of genomic DNA, indicates that these comprise two distinct baboon SP-A genes. Sequence comparison of DNA upstream of the transcription initiation sites and within the 3'-untranslated regions encoded by exon VI indicates that one of the baboon SP-A genes (bSP-A1) is more similar to hSP-A1, whereas the other (bSP-A2) is more similar to hSP-A2. Primer extension analysis of baboon lung mRNA indicates that both baboon SP-A genes utilize conserved transcription initiation sites. Reverse transcriptase-polymerase chain reaction analysis of RNA isolated from lung tissues of fetal baboons of 160 days gestational age indicates that both bSP-A1 and bSP-A2 are expressed in baboon fetal lung and that mRNA transcripts of bSP-A1 and bSP-A2 genes are primarily comprised of sequences encoded by exons I and III-VI. However, minor transcripts of the bSP-A1 gene containing exon II and exon II plus an extension also were detected. The presence of two SP-A genes in the baboon suggests that duplication of the SP-A gene occurred > 26.5 million years ago, before divergence of the baboon lineage from the man-gorilla-chimpanzee clade.

11β-Hydroxysteroid dehydrogenase type 2 and the regulation of surfactant protein A by dexamethasone metabolites

2006 ◽  
Vol 290 (4) ◽  
pp. E653-E660 ◽  
Author(s):  
Mark R. Garbrecht ◽  
Thomas J. Schmidt ◽  
Zygmunt S. Krozowski ◽  
Jeanne M. Snyder
Keyword(s):  
Human Lung ◽  
Protein A ◽  
Fetal Lung ◽  
Hydroxysteroid Dehydrogenase ◽  
Surfactant Protein ◽  
Biologically Active ◽  
Surfactant Protein A ◽  
Human Adult ◽  
Sensitive Organ ◽  
Lung Epithelial

Glucocorticoid (GC) metabolism by the 11β-hydroxysteroid dehydrogenase (HSD) system is an important prereceptor regulator of GC action. The HSD enzymes catalyze the interconversion of the endogenous, biologically active GC cortisol and its inactive 11-dehydro metabolite cortisone. The role of the HSD enzymes in the metabolism of synthetic GCs, such as dexamethasone (Dex), is more complex. The human lung is a classic GC-sensitive organ; however, the roles of the HSD enzymes (HSD1 and HSD2) in the human lung are poorly understood. In the present study, we examined the expression of the HSD enzymes in human adult and fetal lung tissues and the human lung epithelial cell line NCI-H441. We observed that human adult and fetal lung tissues, as well as H441 cells, express HSD2 protein and that it is upregulated by Dex (10−7 M). By contrast, HSD1 protein was undetectable. We also show that the Dex-mediated regulation of surfactant protein A is attenuated by inhibition of HSD2 activity. Furthermore, we demonstrate that unlike the inactive, 11-dehydro metabolite of cortisol (i.e., cortisone), the 11-dehydro metabolite of Dex, 11-dehydro-Dex, competes for binding to the GC receptor (GR) in human lung epithelial cells and retains GR agonist activity. Together, these data suggest that differences exist in the biological activities of the metabolites of cortisol and Dex.

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