Source:http://linkedlifedata.com/resource/pubmed/id/16916954
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
11
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pubmed:dateCreated |
2006-10-17
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pubmed:abstractText |
Surfactant protein-A (SP-A) gene expression is developmentally regulated in fetal lung type II cells in concert with surfactant glycerophospholipid synthesis. In studies using transfected type II cells, we characterized a nuclear receptor element (NRE(SP-A), 5'-TGACCTTA-3') at -242 bp in the 5'-flanking sequence of human SP-A2 (hSP-A) gene that is essential for basal and cAMP-induced expression. NRE(SP-A) has high sequence similarity to the consensus binding site for estrogen-related receptor (ERR). In the present study, we observed that ERRalpha and ERRgamma, but not ERRbeta, were expressed in human fetal lung type II cells. In vitro transcribed/translated ERRalpha and ERRgamma bound to the NRE(SP-A); DNase I footprinting using bacterially expressed ERRalpha revealed a single DNase I protected region that included NRE(SP-A). In transient transfection assays of COS-7 and primary cultures of lung type II cells, ERRalpha acting through NRE(SP-A) increased hSP-A promoter activity, whereas ERRgamma had no effect. ERRalpha overexpression in lung type II cells enhanced cAMP induction of endogenous hSP-A expression, whereas cotransfection of protein kinase A catalytic subunit enhanced ERRalpha stimulation of hSP-A promoter activity in lung adenocarcinoma cells. Mice homozygous null for the ERRalpha gene manifested decreased SP-A expression relative to wild-type and heterozygous littermates. The ERRalpha-specific inverse agonist XCT790 inhibited cAMP induced hSP-A expression in human fetal lung type II cells in a concentration-dependent manner, suggesting a role of peroxisome proliferator-activated receptor-gamma coactivator 1alpha. These findings suggest that ERRalpha acting through NRE(SP-A) is an important mediator of hSP-A gene expression and its induction by cAMP.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/ERRalpha estrogen-related receptor,
http://linkedlifedata.com/resource/pubmed/chemical/ESRRG protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nitriles,
http://linkedlifedata.com/resource/pubmed/chemical/Pulmonary Surfactant-Associated...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Estrogen,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazoles,
http://linkedlifedata.com/resource/pubmed/chemical/XCT790
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0013-7227
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
147
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5187-95
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:16916954-Cells, Cultured,
pubmed-meshheading:16916954-Cyclic AMP,
pubmed-meshheading:16916954-Fetus,
pubmed-meshheading:16916954-Gene Expression Regulation,
pubmed-meshheading:16916954-Humans,
pubmed-meshheading:16916954-Lung,
pubmed-meshheading:16916954-Nitriles,
pubmed-meshheading:16916954-Promoter Regions, Genetic,
pubmed-meshheading:16916954-Pulmonary Surfactant-Associated Protein A,
pubmed-meshheading:16916954-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:16916954-Receptors, Estrogen,
pubmed-meshheading:16916954-Thiazoles
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pubmed:year |
2006
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pubmed:articleTitle |
Estrogen related receptor-alpha enhances surfactant protein-A gene expression in fetal lung type II cells.
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pubmed:affiliation |
Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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