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Ionizing irradiation increases transcription of the von Willebrand factor
gene in endothelial cells
N Jahroudi, AM Ardekani and JS Greenberger
Department of Radiation Oncology, University of Pittsburgh Medical Center,
PA 15213, USA.
Ionizing irradiation damage to the vasculature results in an increase in
procoagulant activity of endothelial cells, including elevated von
Willebrand factor (vWf) secretion. We investigated the mechanism of
irradiation induction of vWf release and demonstrated that vWf mRNA levels
were increased when either human or bovine endothelial cells were exposed
to 20 Gy irradiation. This response to irradiation was independent to de
novo protein synthesis, but required new transcription. Nuclear run-on
experiments indicated that increased vWf transcriptional activity was
partly responsible for the higher levels of the mRNA accumulation.
Transfection analyses with plasmids in which a human growth hormone
structural gene was under the control of the endothelial-cell-specific vWf
promoter demonstrated that irradiation increased promoter activity.
Deletion analyses demonstrated that sequences necessary for irradiation
induction of the promoter activity were located within the 112-bp sequences
(-90 to +22) that constitute the non-endothelial-cell-specific core
promoter region of the vWf gene. Results of gel mobility assays and
deletion analyses demonstrated that a site in the vWf promoter other than
the putative NF-kB binding site is involved in the mechanism of irradiation
induction of the vWf.
Volume 88,
Issue 10,
pp. 3801-3814,
11/15/1996
Copyright © 1996 by The American Society of Hematology

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