PMID- 9705358
OWN - NLM
STAT- MEDLINE
DCOM- 19980917
LR  - 20220311
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 273
IP  - 34
DP  - 1998 Aug 21
TI  - Tumor necrosis factor-alpha regulates expression of vascular endothelial growth 
      factor receptor-2 and of its co-receptor neuropilin-1 in human vascular 
      endothelial cells.
PG  - 22128-35
AB  - 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.
FAU - Giraudo, E
AU  - Giraudo E
AD  - Vascular Biology Laboratory, Department of Genetics, Biology and Biochemistry, 
      Medical School, University of Torino, Torino, 10126 Italy.
FAU - Primo, L
AU  - Primo L
FAU - Audero, E
AU  - Audero E
FAU - Gerber, H P
AU  - Gerber HP
FAU - Koolwijk, P
AU  - Koolwijk P
FAU - Soker, S
AU  - Soker S
FAU - Klagsbrun, M
AU  - Klagsbrun M
FAU - Ferrara, N
AU  - Ferrara N
FAU - Bussolino, F
AU  - Bussolino F
LA  - eng
GR  - 45548/PHS HHS/United States
GR  - CA 37392/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antigens, Surface)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Growth Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 144713-63-3 (Neuropilin-1)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor)
SB  - IM
MH  - Antigens, Surface/*metabolism
MH  - Cells, Cultured
MH  - Endothelium, Vascular/*metabolism
MH  - Gene Expression Regulation
MH  - Humans
MH  - Kinetics
MH  - Membrane Glycoproteins/*metabolism
MH  - Nerve Tissue Proteins/genetics/*metabolism
MH  - Neuropilin-1
MH  - RNA, Messenger/metabolism
MH  - Receptor Protein-Tyrosine Kinases/genetics/*metabolism
MH  - Receptors, Cell Surface/*metabolism
MH  - Receptors, Growth Factor/genetics/*metabolism
MH  - Receptors, Vascular Endothelial Growth Factor
MH  - Tumor Necrosis Factor-alpha/*physiology
MH  - Up-Regulation
MH  - Wound Healing
EDAT- 1998/08/15 00:00
MHDA- 1998/08/15 00:01
CRDT- 1998/08/15 00:00
PHST- 1998/08/15 00:00 [pubmed]
PHST- 1998/08/15 00:01 [medline]
PHST- 1998/08/15 00:00 [entrez]
AID - S0021-9258(18)48893-X [pii]
AID - 10.1074/jbc.273.34.22128 [doi]
PST - ppublish
SO  - J Biol Chem. 1998 Aug 21;273(34):22128-35. doi: 10.1074/jbc.273.34.22128.