|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
9
|
|
pubmed:dateCreated |
2006-5-2
|
|
pubmed:abstractText |
This study examines the hypothesis that transforming growth factor beta (TGFbeta) regulates cyclooxygenase-2 (COX-2) and induces prostaglandin E synthase (mPGES-1) in rat mesangial cells. COX-2 expression was determined by Northern blot analysis after treatment with either TGFbeta1 or the selective COX-2 inhibitor, NS398. mPGES-1 expression was determined by real-time polymerase chain reaction. The effect of TGFbeta1 on COX-2 gene transcription was assessed using a luciferase reporter assay, and mRNA stability was also determined. To determine whether TGFbeta1 activates elements of the COX-2 promoter, we performed gel shift analyses to examine activation of activator protein-1 (AP-1) and nuclear factor kappaB (NF-kappaB). Prostaglandin E(2) (PGE(2)) and thromboxane B2 (TxB2) production was assayed by enzyme immunoassay. Finally, the pathophysiological relevance of COX-2 inhibition on the downstream effects of TGFbeta was assessed by examining collagen type I mRNA and net collagen production. COX-2 mRNA and mPGES-1 were induced after treatment with TGFbeta1 for 4 h, and this rise was accompanied by a three-fold increase in PGE(2) production that could be antagonized by selective inhibition of COX-2 with NS398. TGFbeta1 increased transcription by approximately 50% and activated both AP-1 and NF-kappaB. These effects were antagonized by co-treatment with NS398. Treatment with TGFbeta1 also doubled the half-life of COX-2 mRNA. Neither collagen type I mRNA nor net collagen production were altered by co-treatment with NS398. In conclusion, these results indicate that TGFbeta stimulates COX-2 and mPGES-1, with additional effects on transcription and stability of COX-2 mRNA.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Collagen Type I,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2 Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/N-(2-cyclohexyloxy-4-nitrophenyl)met...,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrobenzenes,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/Ptges protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
May
|
|
pubmed:issn |
0085-2538
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
69
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
1578-85
|
|
pubmed:dateRevised |
2008-11-21
|
|
pubmed:meshHeading |
pubmed-meshheading:16572115-Animals,
pubmed-meshheading:16572115-Collagen Type I,
pubmed-meshheading:16572115-Cyclooxygenase 2,
pubmed-meshheading:16572115-Cyclooxygenase 2 Inhibitors,
pubmed-meshheading:16572115-Dinoprostone,
pubmed-meshheading:16572115-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:16572115-Humans,
pubmed-meshheading:16572115-Kidney Glomerulus,
pubmed-meshheading:16572115-Mesangial Cells,
pubmed-meshheading:16572115-NF-kappa B,
pubmed-meshheading:16572115-Nitrobenzenes,
pubmed-meshheading:16572115-Promoter Regions, Genetic,
pubmed-meshheading:16572115-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:16572115-RNA, Messenger,
pubmed-meshheading:16572115-RNA Stability,
pubmed-meshheading:16572115-Rats,
pubmed-meshheading:16572115-Rats, Sprague-Dawley,
pubmed-meshheading:16572115-Sulfonamides,
pubmed-meshheading:16572115-Transcription, Genetic,
pubmed-meshheading:16572115-Transcription Factor AP-1,
pubmed-meshheading:16572115-Transforming Growth Factor beta
|
|
pubmed:year |
2006
|
|
pubmed:articleTitle |
Transforming growth factor beta regulates cyclooxygenase-2 in glomerular mesangial cells.
|
|
pubmed:affiliation |
Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, Virginia, USA. phardin1@hfhs.org
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
