scholarly journals Developmental and hormonal regulation of surfactant protein C (SP-C) gene expression in fetal lung. Role of transcription and mRNA stability.

1994 ◽  
Vol 269 (44) ◽  
pp. 27767-27772
Author(s):  
V Boggaram ◽  
R K Margana
Keyword(s):  
Gene Expression ◽  
Mrna Stability ◽  
Hormonal Regulation ◽  
Protein C ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Surfactant Protein C

Rabbit surfactant protein C: cDNA cloning and regulation of alternatively spliced surfactant protein C mRNAs

1992 ◽  
Vol 263 (6) ◽  
pp. L634-L644 ◽  
Author(s):  
V. Boggaram ◽  
R. K. Margana
Keyword(s):  
Gene Expression ◽  
Lung Development ◽  
Genomic Dna ◽  
Protein C ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Surfactant Protein C ◽  
Fetal Lung Development ◽  
Mrna Content

Surfactant protein C (SP-C), a hydrophobic protein of pulmonary surfactant is essential for surfactant function. Toward elucidating molecular mechanisms that mediate regulation of SP-C gene expression in rabbit lung, we isolated and characterized cDNAs encoding rabbit SP-C and studied the regulation of SP-C gene expression during fetal lung development and by adenosine 3',5'-cyclic monophosphate (cAMP) and dexamethasone in fetal lung tissues in vitro. We found that rabbit SP-C is highly homologous to SP-C of other species and is encoded by two mRNAs that differ by an insertion of 31 nucleotides in the 3' untranslated regions. SP-C mRNAs were classified into two types based on the nucleotide sequence; type I represents RNA without the 31 nucleotide insert and comprises approximately 80–90% of total SP-C mRNA content, whereas type II represents RNA containing the insert and comprises approximately 10–20% of total SP-C mRNA content. SP-C mRNAs were induced in a coordinate manner during fetal lung development and by cAMP and dexamethasone in fetal lung tissues in vitro. Southern hybridization analysis of genomic DNA suggested that SP-C mRNAs are encoded by a single gene. Polymerase [corrected] chain reaction-amplification of genomic DNA with oligonucleotide primers flanking the insertional sequence and sequence analysis of amplified DNA showed that SP-C mRNAs are produced by alternative use of 3' splice sites of intron 5 of SP-C gene.

scholarly journals Expression and Glucocorticoid Regulation of Surfactant Protein C in Human Fetal Lung

1997 ◽  
Vol 42 (3) ◽  
pp. 356-364 ◽  
Author(s):  
Kola O Solarin ◽  
Philip L Ballard ◽  
Susan H Guttentag ◽  
Catherine A Lomax ◽  
Michael F Beers
Keyword(s):  
Protein C ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Surfactant Protein C ◽  
Human Fetal Lung

The role of pulmonary surfactant protein C during the breathing cycle

1998 ◽  
Vol 327-329 ◽  
pp. 632-635 ◽  
Author(s):  
H.-J. Galla ◽  
N. Bourdos ◽  
A. von Nahmen ◽  
M. Amrein ◽  
M. Sieber
Keyword(s):  
Pulmonary Surfactant ◽  
Protein C ◽  
Surfactant Protein ◽  
Breathing Cycle ◽  
Surfactant Protein C ◽  
Pulmonary Surfactant Protein

scholarly journals Role of CCR2+ Myeloid Cells in Inflammation Responses Driven by Expression of a Surfactant Protein-C Mutant in the Alveolar Epithelium

2021 ◽  
Vol 12 ◽  
Author(s):  
Alessandro Venosa ◽  
Sophie Cowman ◽  
Jeremy Katzen ◽  
Yaniv Tomer ◽  
Brittnie S. Armstrong ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Mrna Expression ◽  
Protein C ◽  
Cell Activation ◽  
Surfactant Protein ◽  
Chronic Obstructive ◽  
Alveolar Type ◽  
Genetic Ablation ◽  
Surfactant Protein C

Acute inflammatory exacerbations (AIE) represent precipitous deteriorations of a number of chronic lung conditions, including pulmonary fibrosis (PF), chronic obstructive pulmonary disease and asthma. AIEs are marked by diffuse and persistent polycellular alveolitis that profoundly accelerate lung function decline and mortality. In particular, excess monocyte mobilization during AIE and their persistence in the lung have been linked to poor disease outcome. The etiology of AIEs remains quite uncertain, but environmental exposure and genetic predisposition/mutations have been identified as two contributing factors. Guided by clinical evidence, we have developed a mutant model of pulmonary fibrosis leveraging the PF-linked missense isoleucine to threonine substitution at position 73 [I73T] in the alveolar type-2 cell-restricted Surfactant Protein-C [SP-C] gene [SFTPC]. With this toolbox at hand, the present work investigates the role of peripheral monocytes during the initiation and progression of AIE-PF. Genetic ablation of CCR2+ monocytes (SP-CI73TCCR2KO) resulted in improved lung histology, mouse survival, and reduced inflammation compared to SP-CI73TCCR2WT cohorts. FACS analysis of CD11b+CD64-Ly6Chi monocytes isolated 3 d and 14 d after SP-CI73T induced injury reveals dynamic transcriptional changes associated with “Innate Immunity’ and ‘Extracellular Matrix Organization’ signaling. While immunohistochemical and in situ hybridization analysis revealed comparable levels of tgfb1 mRNA expression localized primarily in parenchymal cells found nearby foci of injury we found reduced effector cell activation (C1q, iNOS, Arg1) in SP-CI73TCCR2KO lungs as well as partial colocalization of tgfb1 mRNA expression in Arg1+ cells. These results provide a detailed picture of the role of resident macrophages and recruited monocytes in the context of AIE-PF driven by alveolar epithelial dysfunction.

Embryonic stem cells form glandular structures and express surfactant protein C following culture with dissociated fetal respiratory tissue

2006 ◽  
Vol 290 (6) ◽  
pp. L1210-L1215 ◽  
Author(s):  
Mark Denham ◽  
Timothy J. Cole ◽  
Richard Mollard
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Protein C ◽  
Single Cells ◽  
Cell Mass ◽  
Embryonic Stem ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Surfactant Protein C ◽  
Visceral Mesoderm

Mouse embryonic stem cells (MESCs) are pluripotent, theoretically immortal cells derived from the inner cell mass of developing blastocysts. The respiratory epithelium develops from the primitive foregut endoderm as a result of inductive morphogenetic interactions with the surrounding visceral mesoderm. After dissociation of the explanted fetal lung into single cells, these morphogenetic signaling pathways instruct reconstitution of the developing lung according to a process known as organotypic regeneration. Data presented here demonstrate that such fetal lung morphogenetic cues induce MESC derivatives to incorporate into the reforming pseudoglandular-like tubular ducts, display pan-keratin and surfactant protein C (Sftpc) immunoreactivity, and express Sftpc transcripts while displaying a normal diploid karyotype in coculture. The Sftpc inductive capacity of dissociated fetal lung tissue shows stage specificity with 24% of all MESC derivatives displaying Sftpc immunoreactivity after coculture with embryonic day 11.5 (E11.5) lung buds compared with 6% and 0.02% following coculture with E12.5 and E13.5 lung buds, respectively. MESC derivative Sftpc immunoreactivity follows a spatial and temporal specific maturation profile with an initially ubiquitous cellular Sftpc immunostaining pattern becoming apically polarized with time. Directing differentiation of MESCs into respiratory lineages has important implications for cell replacement therapeutics aimed at treating respiratory-specific diseases such as cystic fibrosis and idiopathic pulmonary fibrosis.

Surfactant protein C: hormonal control of SP-C mRNA levels in vitro

1992 ◽  
Vol 262 (6) ◽  
pp. L684-L687 ◽  
Author(s):  
S. V. Veletza ◽  
K. V. Nichols ◽  
I. Gross ◽  
H. Lu ◽  
D. W. Dynia ◽  
...  
Keyword(s):  
Hormonal Regulation ◽  
Protein C ◽  
Cdna Probe ◽  
Surfactant Protein ◽  
Hormonal Control ◽  
Mrna Levels ◽  
Cyclic Monophosphate ◽  
Surfactant Protein C ◽  
Dose Dependent Increase ◽  
Dose Dependent

We have studied hormonal regulation of the surfactant protein C (SP-C) in fetal 18-dah rat lung explants. SP-C mRNA was detected in Northern blots with a specific rat SP-C cDNA probe and quantified by densitometry. Treatment of the explants with dexamethasone resulted in a dose-dependent increase of the SP-C mRNA level. Transcriptional assays have shown that the regulation of SP-C mRNA by dexamethasone involves a transcriptional step. Administration of the cAMP analogues, 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) or dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP), produced a dose-dependent increase of SP-C mRNA levels, with maximum stimulation observed at 200 microM. The thyroid hormone T3 had no effect on SP-C mRNA levels, whether administered alone or in combination with dexamethasone. Variation in the effects of the above hormones on three surfactant protein mRNAs, SP-A, SP-B and SP-C, indicates that the hormonal regulation of the surfactant proteins is a complex process and that each gene is, in part, differentially regulated.

Developmental and hormonal regulation of SP-A gene expression in baboon fetal lung

1996 ◽  
Vol 271 (4) ◽  
pp. L609-L616 ◽  
Author(s):  
S. R. Seidner ◽  
M. E. Smith ◽  
C. R. Mendelson
Keyword(s):  
Gene Expression ◽  
Gestational Age ◽  
Hormonal Regulation ◽  
Protein A ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Inhibitory Effect ◽  
Mrna Levels ◽  
Inhibitory Effects ◽  
Lung Maturation

In the present study, we found that surfactant protein A (SP-A) mRNA levels, which are barely detectable in baboon fetal lung at midgestation (92 days), are increased approximately four fold between 125 and 140 days gestation, approximately 7-fold between 140 and 160 days, and approximately 1.5-fold between 160 and 174 days gestation. We also investigated the effects of dibutyryl-adenosine 3',5'-cyclic monophosphate (DB-cAMP) and dexamethasone (Dex) on SP-A gene expression in lung explants from fetal baboons at 92, 125, 140, 160, and 174 days of gestation (term = 184 days). SP-A mRNA levels, which were barely detectable in lung tissues from 92- and 125-day fetal baboons before culture, were induced after incubation for 5 days in serum-free medium and were markedly stimulated by DBcAMP. Dex caused a dose-dependent inhibition of SP-A mRNA levels and antagonized the stimulatory effect of DBcAMP. SP-A mRNA was detectable in lung tissues from 140-day fetal baboons before culture; the levels were further induced after culture and were increased greatly by DBcAMP. Again, Dex antagonized the induction of SP-A mRNA by DBcAMP. The stimulatory effects of DBcAMP and inhibitory effects of Dex on SP-A mRNA levels in lung tissues of 92- to 140-day gestational age fetal baboons were highly similar to those observed in studies using lung explants of midgestation human abortuses. By contrast, SP-A mRNA was present in relatively high levels in lung tissues of 160- and 174-day fetal baboons before culture and was relatively unaffected after incubation for 5 days in control medium. In lung explants from 160- and 174-day fetal baboons, the stimulatory effect of DBcAMP and inhibitory effect of Dex on SP-A mRNA levels were relatively modest compared with the effects of these agents on SP-A mRNA in fetal lung tissues from 92-, 125-, and 140-day gestational age fetuses. These findings suggest that, with increased lung maturation and the developmental induction of SP-A gene expression, there is a decrease in responsiveness of the fetal lung to the stimulatory effects of cAMP and inhibitory effects of glucocorticoids on SP-A gene expression.

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