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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2007-11-30
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pubmed:abstractText |
Concomitant use of hydrocortisone and the nonspecific cyclo-oxygenase (COX)-inhibitor indomethacin increases the risk for intestinal perforations in preterm infants. We determined whether this was associated with insufficient epidermal growth factor receptor (EGF-R) signaling. We tested the effect of EGF, hydrocortisone, and indomethacin on its activation, cell proliferation and migration, COX-2 expression, and prostaglandin E2 (PGE2) production. Human small intestine epithelial cell line FHsInt74 and EGF-R-deficient mice [EGF-R (-/-)] were used as models. The data revealed that EGF-R signaling had a bimodal positive effect on fetal enterocyte: 1) it increased cell proliferation and migration synergistically with hydrocortisone and 2) up-regulated COX-2 mRNA expression and subsequent PGE2 production. Correlating with this, COX-2 protein expression was down-regulated in EGF-R (-/-) intestine. Despite a positive effect on cell proliferation with EGF, hydrocortisone blunted the stimulatory effect of EGF on COX-2 expression and PGE2 production. Addition of indomethacin even further inhibited the EGF-stimulated PGE2 synthesis. The data suggest that concomitant use of indomethacin and hydrocortisone on preterm infants, who physiologically synthesize only low levels of EGF-R ligands, may lead to intestinal problems related to failure in cytoprotective and regenerative events.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/EGFR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrocortisone,
http://linkedlifedata.com/resource/pubmed/chemical/Indomethacin,
http://linkedlifedata.com/resource/pubmed/chemical/PTGS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ptgs2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0031-3998
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
62
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
570-5
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17805209-Animals,
pubmed-meshheading:17805209-Cell Line,
pubmed-meshheading:17805209-Cell Movement,
pubmed-meshheading:17805209-Cell Proliferation,
pubmed-meshheading:17805209-Cyclooxygenase 2,
pubmed-meshheading:17805209-Cyclooxygenase Inhibitors,
pubmed-meshheading:17805209-Dinoprostone,
pubmed-meshheading:17805209-Enterocytes,
pubmed-meshheading:17805209-Epidermal Growth Factor,
pubmed-meshheading:17805209-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:17805209-Humans,
pubmed-meshheading:17805209-Hydrocortisone,
pubmed-meshheading:17805209-Indomethacin,
pubmed-meshheading:17805209-Intestine, Small,
pubmed-meshheading:17805209-Mice,
pubmed-meshheading:17805209-Mice, Knockout,
pubmed-meshheading:17805209-RNA, Messenger,
pubmed-meshheading:17805209-Receptor, Epidermal Growth Factor,
pubmed-meshheading:17805209-Signal Transduction,
pubmed-meshheading:17805209-Up-Regulation
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pubmed:year |
2007
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pubmed:articleTitle |
Hydrocortisone and indomethacin negatively modulate EGF-R signaling in human fetal intestine.
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pubmed:affiliation |
Molecular Cancer Biology Program, University of Helsinki, FIN-00014, Finland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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