rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2000-3-14
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pubmed:abstractText |
Understanding the regulation of genes controlling fibrinolysis and matrix homeostasis is essential for elucidating the basis of tissue repair. A recently described novel Krüppel-like factor, Zf9, is up-regulated in acute liver injury in activated hepatic stellate cells. Because Zf9 can be induced widely, its activity was examined in vascular endothelium, a key cell in vascular injury. Zf9 is induced as an immediate-early response gene in bovine aortic endothelial cells (BAECs) following treatment with serum or phorbol ester. Zf9 transcriptionally activates urokinase plasminogen activator (uPA). Recombinant Zf9-GST binds to wild-type but not mutated 'GC-box' motifs within the human uPA promoter (-63 to -32), with greatest affinity to the middle of 3 contiguous GC boxes. Transient transfection of Zf9 drives transactivation of a full-length uPA promoter- and GC box-construct, but not a uPA promoter-construct devoid of GC boxes. Transactivation of uPA by Zf9 is also supported in Drosophila S2 cells. Most importantly, transiently transfected Zf9 up-regulates endogenous uPA messenger RNA and activity in BAECs, resulting in increased bioactive transforming growth factor-beta (TGF-beta) via enhancement of proteolytic activation of the latent molecule. Furthermore, concomitant expression of Zf9 and uPA proteins was observed in arterial endothelial cells after balloon injury in rats, suggesting a potential role of Zf9 in uPA expression not only in vitro but also in vivo. These findings suggest a role of Zf9 in the injury response by enhancing uPA synthesis and subsequent activation of latent TGF-beta. (Blood. 2000;95:1309-1316)
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Copeb protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Fibrinolysin,
http://linkedlifedata.com/resource/pubmed/chemical/KLF6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Kruppel-Like Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Urokinase-Type Plasminogen Activator
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
95
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1309-16
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10666204-Animals,
pubmed-meshheading:10666204-Aorta,
pubmed-meshheading:10666204-Base Sequence,
pubmed-meshheading:10666204-Binding Sites,
pubmed-meshheading:10666204-Carotid Arteries,
pubmed-meshheading:10666204-Carotid Artery Injuries,
pubmed-meshheading:10666204-Cattle,
pubmed-meshheading:10666204-Cell Line,
pubmed-meshheading:10666204-Cell Membrane,
pubmed-meshheading:10666204-Cells, Cultured,
pubmed-meshheading:10666204-Drosophila melanogaster,
pubmed-meshheading:10666204-Endothelium, Vascular,
pubmed-meshheading:10666204-Fibrinolysin,
pubmed-meshheading:10666204-Gene Expression Regulation,
pubmed-meshheading:10666204-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:10666204-Humans,
pubmed-meshheading:10666204-Kruppel-Like Transcription Factors,
pubmed-meshheading:10666204-Mutagenesis, Site-Directed,
pubmed-meshheading:10666204-Promoter Regions, Genetic,
pubmed-meshheading:10666204-Proto-Oncogene Proteins,
pubmed-meshheading:10666204-Rats,
pubmed-meshheading:10666204-Recombinant Proteins,
pubmed-meshheading:10666204-Trans-Activators,
pubmed-meshheading:10666204-Transcriptional Activation,
pubmed-meshheading:10666204-Transfection,
pubmed-meshheading:10666204-Transforming Growth Factor beta,
pubmed-meshheading:10666204-Urokinase-Type Plasminogen Activator
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pubmed:year |
2000
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pubmed:articleTitle |
Transcriptional activation of urokinase by the Krüppel-like factor Zf9/COPEB activates latent TGF-beta1 in vascular endothelial cells.
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pubmed:affiliation |
Laboratory of Molecular Cell Sciences, Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN), Koyadai, Tsukuba, Ibaraki 305-0074, Japan. kojima@rtc.riken.go.jp
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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