Source:http://linkedlifedata.com/resource/pubmed/id/16868306
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2006-11-3
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pubmed:abstractText |
Epithelial-to-mesenchymal transition (EMT) has emerged as a critical event in the pathogenesis of tubulointerstitial fibrosis. EMT is typically induced by transforming growth factor-beta1 (TGF-beta1) and inhibited by hepatocyte growth factor (HGF). The present study was undertaken to evaluate the potential role of cyclooxygenase (COX)-2-derived PGE2 in regulation of EMT in cultured Madin-Darby canine kidney (MDCK) cells, in the setting of HGF treatment. Exposure to 50 ng/ml HGF significantly induced COX-2 protein expression and PGE2 release, whereas other growth factors, including epidermal growth factor, the insulin-like growth factor I protein, platelet-derived growth factor-BB, and TGF-beta1, had no effects on COX-2 expression or PGE2 release. COX-2 induction by HGF was preceded by activation of ERK1/2, and an ERK1/2-specific inhibitor, U-0126 (10 microM), completely abolished HGF-induced COX-2 expression. Exposure of MDCK cells to 10 ng/ml TGF-beta1 for 72 h induced EMT as evidenced by conversion to the spindle-like morphology, loss of E-cadherin, and activation of alpha-smooth muscle actin. In contrast, treatment with 1 microM PGE2 completely blocked EMT, associated with a significant elevation of intracellular cAMP and complete blockade of TGF-beta1-induced oxidant production. cAMP-elevating agents, including 8-Br-cAMP, forskolin, and IBMX, inhibited EMT and associated oxidative stress induced by TGF-beta1, but inhibition of cAMP pathway with Rp-cAMP, the cAMP analog, and H89, the protein kinase A (PKA) inhibitor, did not block the effect of PGE2. The effect of HGF on EMT was inhibited by approximately 50% in the presence of a COX-2 inhibitor SC-58635 (10 microM). Therefore, our data suggest that PGE2 inhibits EMT via inhibition of oxidant production and COX-2-derived PGE2 partially accounts for the antifibrotic effect of HGF.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Actins,
http://linkedlifedata.com/resource/pubmed/chemical/Cadherins,
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/Hepatocyte Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1,
http://linkedlifedata.com/resource/pubmed/chemical/celecoxib
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1931-857X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
291
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
F1323-31
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pubmed:dateRevised |
2011-4-28
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pubmed:meshHeading |
pubmed-meshheading:16868306-Actins,
pubmed-meshheading:16868306-Animals,
pubmed-meshheading:16868306-Cadherins,
pubmed-meshheading:16868306-Cell Line,
pubmed-meshheading:16868306-Cyclooxygenase 2,
pubmed-meshheading:16868306-Cyclooxygenase Inhibitors,
pubmed-meshheading:16868306-Dinoprostone,
pubmed-meshheading:16868306-Dogs,
pubmed-meshheading:16868306-Drug Interactions,
pubmed-meshheading:16868306-Enzyme Activation,
pubmed-meshheading:16868306-Epithelial Cells,
pubmed-meshheading:16868306-Fibrosis,
pubmed-meshheading:16868306-Hepatocyte Growth Factor,
pubmed-meshheading:16868306-Kidney Failure, Chronic,
pubmed-meshheading:16868306-Kidney Tubules,
pubmed-meshheading:16868306-MAP Kinase Signaling System,
pubmed-meshheading:16868306-Mesoderm,
pubmed-meshheading:16868306-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:16868306-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:16868306-Pyrazoles,
pubmed-meshheading:16868306-Sulfonamides,
pubmed-meshheading:16868306-Transforming Growth Factor beta1
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pubmed:year |
2006
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pubmed:articleTitle |
Prostaglandin E2 is a potent inhibitor of epithelial-to-mesenchymal transition: interaction with hepatocyte growth factor.
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pubmed:affiliation |
Division of Nephrology, University of Utah and VA Medical Center, Salt Lake City, UT 84148, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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