Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2000-3-14
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)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
95
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1309-16
pubmed:dateRevised
2009-11-19
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
pubmed:year
2000
pubmed:articleTitle
Transcriptional activation of urokinase by the Krüppel-like factor Zf9/COPEB activates latent TGF-beta1 in vascular endothelial cells.
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
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't