Source:http://linkedlifedata.com/resource/pubmed/id/12711254
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2003-4-24
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pubmed:abstractText |
We tested the hypothesis that in endothelial cells, chronic arterial shear stress represses both the transactivator nuclear factor-kappaB (NF-kappaB) and subsequent platelet-derived growth factor (PDGF)-B gene transcription. Bovine aortic endothelial (BAE) and glomerular capillary endothelial (GEN) cells were subjected to chronic (9 days) arterial shear stress (10 dyne/cm(2)). Chronic shear stress reduced PDGF-B transcripts in BAE cells by 59 +/- 23% compared to controls, and by 70 +/- 14% in GEN cells. While PDGF-B mRNA levels were not significantly changed in BAE cells subjected to acute (4 h) shear stress, in GEN cells PDGF-B transcript abundance fell by 59 +/- 3%. PDGF-B mRNA stability was unchanged. We investigated the possibility that these effects were due to decreased nuclear NF-kappaB. NF-kappaB levels were much lower in nuclei of chronic shear stress-treated cells compared to controls. This represents classical inactivation of NF-kappaB since cytoplasmic NF-kappaB/I-kappaB (the inhibitory protein of NF-kappaB) levels were elevated in shear stress-treated cells. Further supporting NF-kappaB regulation of PDGF-B, activation of NF-kappaB by interleukin (IL)-1beta resulted in increased PDGF-B transcript levels. Treatment of cells with MG-132, an inhibitor of NF-kappaB activation, resulted in a dramatic decrease in basal PDGF-B transcript levels, and essentially abrogated the response to IL-1beta. Thus, repression of NF-kappaB activation in endothelial cells by shear stress decreases PDGF-B gene expression, while activators of NF-kappaB increase PDGF-B transcription.
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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/Leupeptins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-sis,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonylleucyl-leucyl-leuci...
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0026-2862
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
65
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
137-44
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:12711254-Animals,
pubmed-meshheading:12711254-Aorta,
pubmed-meshheading:12711254-Blotting, Northern,
pubmed-meshheading:12711254-Capillaries,
pubmed-meshheading:12711254-Cattle,
pubmed-meshheading:12711254-Cell Nucleus,
pubmed-meshheading:12711254-Cytoplasm,
pubmed-meshheading:12711254-Endothelial Cells,
pubmed-meshheading:12711254-Glomerular Mesangium,
pubmed-meshheading:12711254-Immunoblotting,
pubmed-meshheading:12711254-Leupeptins,
pubmed-meshheading:12711254-NF-kappa B,
pubmed-meshheading:12711254-Proto-Oncogene Proteins c-sis,
pubmed-meshheading:12711254-RNA,
pubmed-meshheading:12711254-RNA, Messenger,
pubmed-meshheading:12711254-Stress, Mechanical,
pubmed-meshheading:12711254-Time Factors,
pubmed-meshheading:12711254-Transcription, Genetic
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pubmed:year |
2003
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pubmed:articleTitle |
Diminished NF-kappaB activation and PDGF-B expression in glomerular endothelial cells subjected to chronic shear stress.
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pubmed:affiliation |
Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. e-eng@northwestern.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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