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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-4-24
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0026-2862
pubmed:author
pubmed:issnType
Print
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
137-44
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Diminished NF-kappaB activation and PDGF-B expression in glomerular endothelial cells subjected to chronic shear stress.
pubmed:affiliation
Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. e-eng@northwestern.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.