Transcription Factor C/EBPδ in Fetal Lung: Developmental Regulation and Effects of Cyclic Adenosine 3′,5′-Monophosphate and Glucocorticoids1
Pulmonary surfactant is a developmentally and hormonally regulated lipoprotein synthesized exclusively in alveolar type II cells. Surfactant protein-A (SP-A) gene transcription in human fetal lung in culture is stimulated by glucocorticoids and cAMP; cAMP also enhances the rate of type II cell diffe...
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Published in | Endocrinology (Philadelphia) Vol. 138; no. 12; pp. 5527 - 5534 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Endocrine Society
01.12.1997
|
Online Access | Get full text |
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Summary: | Pulmonary surfactant is a developmentally and hormonally regulated
lipoprotein synthesized exclusively in alveolar type II cells.
Surfactant protein-A (SP-A) gene transcription in human fetal lung in
culture is stimulated by glucocorticoids and cAMP; cAMP also enhances
the rate of type II cell differentiation. The CCAAT/enhancer-binding
protein (C/EBP) family of transcription factors serves an important
role in the regulation of genes involved in energy metabolism, lipid
biosynthesis, and cellular differentiation. The gene encoding C/EBPδ,
which is induced by glucocorticoids during the early phases of
adipocyte differentiation, is expressed at relatively high levels in
lung compared with other tissues. In the present study we have analyzed
developmental changes in C/EBPδ messenger RNA levels in fetal rabbit
lung as well as changes in the levels of immunoreactive C/EBPδ in
human fetal lung during differentiation in organ culture and after
treatment with cAMP and glucocorticoids. We observed that C/EBPδ
messenger RNA is detectable in fetal rabbit lung on day 19 of gestation
and is increased ∼3.7-fold to maximum levels on day 28 of gestation,
the time when SP-A gene transcription increases to maximum levels.
Immunohistochemical analysis of C/EBPδ in midgestation human fetal
lung before culture revealed trace nuclear staining in epithelial and
occasional stromal cells. After 12 h of organ culture in
serum-free medium, nuclear staining of C/EBPδ was markedly increased
in epithelial cells lining the prealveolar ducts of the human fetal
lung tissue. By immunoblot analysis, it was found that C/EBPδ levels
were induced rapidly during organ culture in control medium and were
increased further by treatment with dexamethasone and
(Bt)2cAMP. C/EBPδ levels were maximally induced during
the first 24 h of culture and declined thereafter; after 72 h
of incubation in control or cAMP-containing medium, C/EBPδ was
reduced markedly. By contrast, in fetal lung tissues incubated in
medium containing dexamethasone or dexamethasone plus
(Bt)2cAMP, the decline in C/EBPδ was more modest, so that
levels remained elevated throughout the 96-h culture period. Our
findings that C/EBPδ is localized primarily to alveolar epithelial
cells, rapidly induced during differentiation of human fetal lung in
culture, and increased by cAMP and glucocorticoids suggest a possible
role in the regulation of type II cell differentiation and in the
synthesis of surfactant phospholipids and proteins. |
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ISSN: | 0013-7227 1945-7170 |
DOI: | 10.1210/endo.138.12.5637 |