TGF-β3-null mutation does not abrogate fetal lung maturation in vivo by glucocorticoids

1999 ◽  
Vol 277 (6) ◽  
pp. L1205-L1213 ◽  
Author(s):  
Wei Shi ◽  
Nora Heisterkamp ◽  
John Groffen ◽  
Jingsong Zhao ◽  
David Warburton ◽  
...  
Keyword(s):  
Protein C ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Mutant Mice ◽  
Lung Fibroblasts ◽  
Null Mutant ◽  
Lung Maturation ◽  
Surfactant Protein C ◽  
Null Mutant Mice ◽  
Fetal Lung Maturation

Newborn transforming growth factor (TGF)-β3-null mutant mice exhibit defects of palatogenesis and pulmonary development. Glucocorticoids, which play a central role in fetal lung maturation, have been postulated to mediate their stimulatory effects on tropoelastin mRNA expression through TGF-β3 in cultured lung fibroblasts. In the present study, we analyzed the abnormally developed lungs in TGF-β3-null mutant mice and compared the effects of glucocorticoids on gene expression and lung morphology between TGF-β3 knockout and wild-type mice. Lungs of TGF-β3-null mutant mice on embryonic day 18.5 did not form normal saccular structures and had a thick mesenchyme between terminal air spaces. Moreover, the number of surfactant protein C-positive cells was decreased in TGF-β3-null mutant lungs. Interestingly, glucocorticoids were able to promote lung maturation and increased expression of both tropoelastin and fibronectin but decreased the relative number of surfactant protein C-positive cells in fetal lungs of both genotypes. This finding provides direct evidence that glucocorticoid signaling in the lung can use alternative pathways and can exert its effect without the presence of TGF-β3.

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

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.

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.

Intra-amniotic injection of IL-1 induces inflammation and maturation in fetal sheep lung

2002 ◽  
Vol 282 (3) ◽  
pp. L411-L420 ◽  
Author(s):  
Karen E. Willet ◽  
Boris W. Kramer ◽  
Suhas G. Kallapur ◽  
Machiko Ikegami ◽  
John P. Newnham ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Lung Function ◽  
Lung Inflammation ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Lung Compliance ◽  
Fetal Membranes ◽  
Lung Maturation ◽  
Fetal Sheep ◽  
Fetal Lung Maturation

Antenatal inflammation may be an important triggering event in the pathogenesis of bronchopulmonary dysplasia but may also accelerate fetal lung maturation. We examined the effects of intra-amniotic (IA) interleukin (IL)-1α and IL-1β on maturation of the fetal sheep lung. These cytokine effects were compared with IA endotoxin, a potent proinflammatory stimulus that accelerated lung maturation. Date-bred ewes received 15 or 150 μg recombinant ovine IL-1α or IL-1β or 10 mg Escherichia coli endotoxin by IA injection at 118 days gestation (term = 150 days), and fetuses were delivered at 125 days. IL-1α and IL-1β improved lung function and increased alveolar saturated phosphatidylcholine (Sat PC) and surfactant protein mRNA expression at the higher dose. The maturation response to IL-1α was greater than that to IL-1β, which was similar to endotoxin response. Inflammation was also more pronounced after IL-1α treatment. Only endotoxin animals had residual inflammation of the fetal membranes at 7 days. Lung compliance, lung volume, and alveolar Sat PC were positively correlated with residual alveolar wash leukocyte numbers 7 days after IL-1 treatment, suggesting a link between lung inflammation and maturation.

Prostaglandin E2 integrates the effects of fluid distension and glucocorticoid on lung maturation

1998 ◽  
Vol 274 (1) ◽  
pp. L106-L111 ◽  
Author(s):  
J. S. Torday ◽  
H. Sun ◽  
J. Qin
Keyword(s):  
Fetal Lung ◽  
Explant Culture ◽  
Lung Fibroblasts ◽  
Type Ii Cells ◽  
Type Ii ◽  
Lung Maturation ◽  
Fetal Rat ◽  
Surfactant Production ◽  
Type Ii Cell ◽  
Fetal Lung Maturation

Both glucocorticoids and alveolar fluid distension affect the rate of fetal lung maturation, possibly representing a common cellular pathway. In an explant culture, there is a spontaneous increase in triglyceride incorporation into saturated phosphatidylcholine over time. This mechanism is stimulated by prostaglandin (PG) E2, blocked by both bumetanide and indomethacin, and overridden by exogenous PGE2. Type II cells synthesized and produced PGE2 between days 16 and 21 postconception, increasing fourfold between days 19 and 21. Fetal rat lung fibroblasts released triglyceride in response to PGE2, increasing 10- to 14-fold between days 19 and 21 postconception; phloretin (1 × 10−5 M) completely blocked this effect of PGE2 on triglyceride release. Dexamethasone stimulated both type II cell PGE2 synthesis (threefold) and fibroblast triglyceride release in response to PGE2 (60%) by day 20 cells. Stretching type II cells also increased PGE2 synthesis (∼100% at 1, 2, and 3 h vs. static cultures). Recombination of [3H]triglyceride-labeled fibroblasts with type II cells in an organotypic culture resulted in progressive incorporation of label into saturated phosphatidylcholine by type II cells. This process was also blocked by the addition of indomethacin and overridden by exogenous PGE2. These data suggest that the combined effects of alveolar fluid dilatation and glucocorticoids may coordinate the timely transfer of triglyceride from fibroblasts to type II cells for augmented surfactant production through their effects on PGE2 production and action as term approaches.

Homozygous mutation in ABCA3 Lipid-Transporter defect (EXON 9) and low level of surfactant protein C

2010 ◽  
Vol 222 (S 01) ◽  
Author(s):  
J Pöschl ◽  
P Ruef ◽  
M Griese ◽  
P Lohse ◽  
C Aslanidis ◽  
...  
Keyword(s):  
Protein C ◽  
Surfactant Protein ◽  
Homozygous Mutation ◽  
Surfactant Protein C ◽  
Low Level ◽  
Exon 9 ◽  
Lipid Transporter
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