Surfactant protein B processing in human fetal lung

1998 ◽  
Vol 275 (3) ◽  
pp. L559-L566 ◽  
Author(s):  
Susan H. Guttentag ◽  
Michael F. Beers ◽  
Bert M. Bieler ◽  
Philip L. Ballard
Keyword(s):  
Polyclonal Antibodies ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Explant Culture ◽  
Normal Lung ◽  
Surfactant Protein B ◽  
Multistep Process ◽  
Human Fetal Lung ◽  
Protein B

Surfactant protein B (SP-B8), an 8-kDa hydrophobic protein essential for surfactant and normal lung function, is produced from the intracellular processing of preproSP-B. To characterize SP-B processing in human type 2 cells, we used human fetal lung in explant culture and polyclonal antibodies to human SP-B8(Phe201–Met279) and to specific epitopes within the NH2- and COOH-terminal propeptide domains (Ser145–Leu160, Gln186–Gln200, and Gly284–Ser304). Western blot analysis revealed a novel intermediate at ∼9 kDa, representing mature SP-B8, with a residual NH2-terminal peptide of ∼10 amino acids. Pulse-chase studies showed a precursor-product relationship between the 9- and 8-kDa forms. During differentiation of type 2 cells in explant culture, the rate of proSP-B conversion to 25-kDa intermediate remained constant, whereas the rate of 25-kDa intermediate conversion to SP-B8increased, resulting in a net increase in tissue SP-B8. Dexamethasone did not affect the rate of proSP-B processing but markedly enhanced the rate of SP-B8 accumulation. We conclude that NH2-terminal propeptide cleavage of proSP-B is a multistep process and that more distal processing events are rate limiting and both developmentally and hormonally regulated.

Human surfactant protein B promoter in transgenic mice: temporal, spatial, and stimulus-responsive regulation

2002 ◽  
Vol 282 (3) ◽  
pp. L394-L404 ◽  
Author(s):  
Marlene Strayer ◽  
Rashmin C. Savani ◽  
Linda W. Gonzales ◽  
Aisha Zaman ◽  
Zheng Cui ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Transforming Growth Factor ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Explant Culture ◽  
Developmental Expression ◽  
Alveolar Type ◽  
Similar Time ◽  
Surfactant Protein B ◽  
Protein B

Surfactant protein B (SP-B) is a developmentally and hormonally regulated lung protein that is required for normal surfactant function. We generated transgenic mice carrying the human SP-B promoter (−1,039/+431 bp) linked to chloramphenicol acetyltransferase (CAT). CAT activity was high in lung and immunoreactive protein localized to alveolar type II and bronchiolar epithelial cells. In addition, thyroid, trachea, and intestine demonstrated CAT activity, and each of these tissues also expressed low levels of SP-B mRNA. Developmental expression of CAT activity and SP-B mRNA in fetal lung were similar and both increased during explant culture. SP-B mRNA but not CAT activity decreased during culture of adult lung, and both were reduced by transforming growth factor (TGF)-β1. Treatment of adult mice with intratracheal bleomycin caused similar time-dependent decreases in lung SP-B mRNA and CAT activity. These findings indicate that the human SP-B promoter fragment directs tissue- and lung cell-specific transgene expression and contains cis-acting elements involved in regulated expression during development, fetal lung explant culture, and responsiveness to TGF-β and bleomycin-induced lung injury.

scholarly journals Surfactant Protein B in Human Fetal Lung: Developmental and Glucocorticoid Regulation

1995 ◽  
Vol 38 (5) ◽  
pp. 668-675 ◽  
Author(s):  
Michael F Beers ◽  
Henry Shuman ◽  
Helen G Liley ◽  
Joanna Floros ◽  
Linda W Gonzales ◽  
...  
Keyword(s):  
Fetal Lung ◽  
Surfactant Protein ◽  
Surfactant Protein B ◽  
Human Fetal Lung ◽  
Protein B

scholarly journals Dinucleotide repeats in the human surfactant protein-B gene and respiratory-distress syndrome

1995 ◽  
Vol 305 (2) ◽  
pp. 583-590 ◽  
Author(s):  
J Floros ◽  
S V Veletza ◽  
P Kotikalapudi ◽  
L Krizkova ◽  
A M Karinch ◽  
...  
Keyword(s):  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Surfactant Protein ◽  
Normal Lung ◽  
Dinucleotide Repeats ◽  
Conserved Sequence ◽  
Surfactant Protein B ◽  
Genomic Dnas ◽  
Protein B

Pulmonary surfactant, a lipoprotein complex, is essential for normal lung function, and deficiency of surfactant can result in respiratory-distress syndrome (RDS) in the prematurely born infant. Some studies have pointed towards a genetic contribution to the aetiology of RDS. Because the surfactant protein B (SP-B) is important for optimal surfactant function and because it is involved in the pathogenesis of pulmonary disease, we investigated the genetic variability of the SP-B gene in individuals with and without RDS. We identified a 2.5 kb BamHI polymorphism and studied its location, nature and frequency. We localized this polymorphism in the first half of intron 4 and found that it is derived by gain or loss in the number of copies of a motif that consists of two elements, a 20 bp conserved sequence and a variable number of CA dinucleotides. Variability in the number of motifs resulting from either deletion (in 55.3% of the cases with the variation) or insertion (44.7%) of motifs was observed in genomic DNAs from unrelated individuals. Analysis of 219 genomic DNAs from infants with (n = 82) and without (n = 137) RDS showed that this insertion/deletion appears with significantly higher frequency in the RDS population (29.3 as against 16.8%, P < 0.05).

scholarly journals Subcellular Localization Of Surfactant Protein-B (SP-B) Processing Events In Human Type 2 Alveolar Cells • 270

1998 ◽  
Vol 43 ◽  
pp. 49-49 ◽  
Author(s):  
Susan H Guttentag ◽  
Annapurna D Kormilli ◽  
Bo Xing ◽  
Michael F Beers ◽  
Philip L Ballard
Keyword(s):  
Subcellular Localization ◽  
Surfactant Protein ◽  
Alveolar Cells ◽  
Human Type ◽  
Surfactant Protein B ◽  
Protein B

scholarly journals Neuregulin Receptor ErbB4 Functions as a Transcriptional Cofactor for the Expression of Surfactant Protein B in the Fetal Lung

2011 ◽  
Vol 45 (4) ◽  
pp. 761-767 ◽  
Author(s):  
Katja Zscheppang ◽  
Thilo Dörk ◽  
Andreas Schmiedl ◽  
Frank E. Jones ◽  
Christiane E. L. Dammann
Keyword(s):  
Fetal Lung ◽  
Surfactant Protein ◽  
Surfactant Protein B ◽  
Protein B

scholarly journals Surfactant Protein B Intron 4 Variation in German Patients with COPD and Acute Respiratory Failure

2002 ◽  
Vol 18 (3) ◽  
pp. 129-136 ◽  
Author(s):  
Carola Seifart ◽  
Alexandra Plagens ◽  
Dörte Brödje ◽  
Bernd Müller ◽  
Peter von Wichert ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Acute Respiratory Failure ◽  
Pulmonary Disease ◽  
Surfactant Protein ◽  
Normal Lung ◽  
Major Health Problem ◽  
Surfactant Protein B ◽  
Increased Risk ◽  
Intron 4 ◽  
Protein B

Chronic obstructive pulmonary disease (COPD) is a major health problem. Genetic factors that contribute to the disease have been postulated. The pulmonary surfactant protein B (SP-B), which is essential for normal lung function, is considered as a candidate gene for COPD in this case-control study. We studied the SP-B intron 4 size variants in 346 individuals. This group consisted of 118 patients with chronic bronchitis or COPD, including 24 patients with acute respiratory failure (ARF) in COPD, 118 matched controls without pulmonary disease and 110 healthy individuals (population control). The frequency of intron 4 variants was similar in either control group (10.9%, 14.4% respectively), with a small increase in the COPD group (18.6%). This increase was due to a high increase of intron 4 variants in the ARF subgroup (37.5%,p= 0.003, OR 4.9, 95% CI: 1.76–13.6). The data indicate that SP-B intron 4 variants may associate with increased risk of ARF in COPD and may be used as a marker of susceptibility in this disease subgroup.

Transcription and mRNA stability regulate developmental and hormonal expression of rabbit surfactant protein B gene

1995 ◽  
Vol 268 (3) ◽  
pp. L481-L490 ◽  
Author(s):  
R. K. Margana ◽  
V. Boggaram
Keyword(s):  
Gene Transcription ◽  
Mrna Stability ◽  
Lung Development ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Mrna Levels ◽  
Fetal Lung Development ◽  
Surfactant Protein B ◽  
Protein B

Surfactant protein B (SP-B), a hydrophobic protein of pulmonary surfactant, is essential for the surface tension-reducing properties of surfactant. In the present study, we isolated and characterized cDNAs encoding rabbit SP-B, and used transcription run-on assays and Northern blot analysis to investigate the role of transcriptional and posttranscriptional mechanisms in the developmental and cAMP and dexamethasone induction of SP-B mRNA. We found two forms of SP-B cDNAs that differed by an insertion of 69 nucleotides in the 3' untranslated regions. We found that transcription across the SP-B gene is nonequimolar and the 3' end of the gene has high levels of antisense transcription. SP-B gene transcription and SP-B mRNA levels increased during fetal lung development. However, increased SP-B mRNA levels could not be accounted for primarily on the basis of increased transcription. These results suggested that enhanced SP-B gene transcription and enhanced SP-B mRNA stability mediate developmental induction of SP-B gene. In rabbit fetal lung in vitro, both dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) and dexamethasone increased SP-B mRNA levels. DBcAMP-dependent increase in SP-B mRNA levels resulted from increased SP-B gene transcription, whereas dexamethasone-dependent increase resulted from combined effects on increased SP-B gene transcription and SP-B mRNA stability. In tissues treated with dexamethasone the half-life (t1/2) of SP-B mRNA increased > 2.5-fold (t1/2 control = 9 h; t1/2 dex-treated = 25 h). These data show that both transcription and mRNA stability regulate induction of SP-B gene expression during fetal lung development and by cAMP and dexamethasone in fetal lung in vitro.

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