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Cited by 272

The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.

Tumor Necrosis Factor-α Regulates Expression of Vascular Endothelial Growth Factor Receptor-2 and of Its Co-receptor Neuropilin-1 in Human Vascular Endothelial Cells

Open access
Giraudo, Enrico, Primo, Luca, Audero, Enrica, Gerber, Hans-Peter, Koolwijk, Pieter, Soker, Shay, Klagsbrun, Michael, Ferrara, Napoleone, Bussolino, Federico·1998·Journal of Biological Chemistry

Abstract

Tumor necrosis factor-alpha (TNF-alpha) modulates gene expression in endothelial cells and is angiogenic in vivo. TNF-alpha does not activate in vitro migration and proliferation of endothelium, and its angiogenic activity is elicited by synthesis of direct angiogenic inducers or of proteases. Here, we show that TNF-alpha up-regulates in a dose- and time-dependent manner the expression and the function of vascular endothelial growth factor receptor-2 (VEGFR-2) as well as the expression of its co-receptor neuropilin-1 in human endothelium. As inferred by nuclear run-on assay and transient expression of VEGFR-2 promoter-based reporter gene construct, the cytokine increased the transcription of the VEGFR-2 gene. Mithramycin, an inhibitor of binding of nuclear transcription factor Sp1 to the promoter consensus sequence, blocked activation of VEGFR-2, suggesting that the up-regulation of the receptor required Sp1 binding sites. TNF-alpha increased the cellular amounts of VEGFR-2 protein and tripled the high affinity 125I-VEGF-A165 capacity without affecting the Kd of ligand-receptor interaction. As a consequence, TNF-alpha enhanced the migration and the wound healing triggered by VEGF-A165. Since VEGFR-2 mediates angiogenic signals in endothelium, our data indicate that its up-regulation is another mechanism by which TNF-alpha is angiogenic and may provide insight into the mechanism of neovascularization as occurs in TNF-alpha-mediated pathological settings.

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Crossref · 10.1074/jbc.273.34.22128

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Metadata

Authors
Giraudo, E., Primo, L., Audero, E., Gerber, H.-P., Koolwijk, P., Soker, S., Klagsbrun, M., Ferrara, N., & Bussolino, F.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1998-08
Volume
273
Issue
34
Pages
22128-22135
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2000771735
Cited by
272
References
58
FWCI
4.84
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Tumor Necrosis Factor-α Regulates Expression of Vascular Endothelial Growth Factor Receptor-2 and of Its Co-receptor Neuropilin-1 in Human Vascular Endothelial Cells. https://app.cochat.ai/papers/10.1074/jbc.273.34.22128
The paper
Giraudo, E., Primo, L., Audero, E., Gerber, H.-P., Koolwijk, P., Soker, S., Klagsbrun, M., Ferrara, N., & Bussolino, F. (1998). Tumor Necrosis Factor-α Regulates Expression of Vascular Endothelial Growth Factor Receptor-2 and of Its Co-receptor Neuropilin-1 in Human Vascular Endothelial Cells. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.273.34.22128

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