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Citations to this article

Downregulation of vascular endothelial growth factor receptors by tumor necrosis factor-alpha in cultured human vascular endothelial cells.
C Patterson, … , M E Lee, E Haber
C Patterson, … , M E Lee, E Haber
Published July 15, 1996
Citation Information: J Clin Invest. 1996;98(2):490-496. https://doi.org/10.1172/JCI118816.
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Downregulation of vascular endothelial growth factor receptors by tumor necrosis factor-alpha in cultured human vascular endothelial cells.

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Abstract

Vascular endothelial growth factor (VEGF) potently stimulates angiogenesis, whereas TNF-alpha has both pro- and anti-angiogenic activity. By measuring thymidine uptake, we found that TNF-alpha blocked a 2.3-fold increase in DNA synthesis induced by VEGF in human endothelial cells. To explore the possibility that the two interact to regulate endothelial cell proliferation, we examined the effect of TNF-alpha on VEGF receptor expression. In venous and arterial endothelial cells, TNF-alpha potently reduced mRNA transcripts of the two VEGF receptors (KDR/flk-1 and flt-1) in a dose- and time-dependent fashion. TNF-alpha at 1 ng/ml induced maximal inhibition of mRNA expression, which fell by approximately 70% after 24 h. TNF-alpha treatment did not significantly affect the KDR/flk-1 half-life but did decrease its rate of transcription to 40% of control. The decrease in KDR/flk-1 mRNA depended partially on new protein synthesis and was abolished by phorbol ester pretreatment. TNF-alpha decreased the amount of 35S-labeled KDR/flk-1 immunoprecipitated by an antibody specific for KDR/flk-1 to 18% of control. We conclude that TNF-alpha downregulates expression of both VEGF receptors in human endothelial cells and that this effect is transcriptional (at least for KDR/flk-1). These data support the hypothesis that TNF-alpha exerts its antiangiogenic effect in part by modulating the VEGF-specific angiogenic pathway.

Authors

C Patterson, M A Perrella, W O Endege, M Yoshizumi, M E Lee, E Haber

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Focal Adhesion Kinase and p130Cas Mediate Both Sarcomeric Organization and Activation of Genes Associated with Cardiac Myocyte Hypertrophy
B Kovac̆ic̆-Milivojević, F Roediger, EA Almeida, CH Damsky, DG Gardner, D Ilić, MC Beckerle
Molecular biology of the cell 2001
Vascular Morphogenesis in the Female Reproductive System
HG Augustin, PA Rogers, ML Iruela-Arispe, SK Smith
2001
Altered focal adhesion regulation correlates with cardiomyopathy in mice expressing constitutively active rac1
MA Sussman, S Welch, A Walker, R Klevitsky, TE Hewett, RL Price, E Schaefer, K Yager
Journal of Clinical Investigation 2000
VEGF/Flk-1 Interaction, a Requirement for Malignant Ascites Recurrence
B Stoelcker, B Echtenacher, HA Weich, H Sztajer, DJ Hicklin, DN Männel
Journal of Interferon & Cytokine Research 2000
Enhanced proliferation and altered intracellular zinc levels in early- and late-passage mouse aorta smooth muscle cells
SK Moon, SD Ha
Biotechnology and Bioprocess Engineering 2000
Negative feedback regulation of reactive oxygen species on AT1 receptor gene expression
G Nickenig, K Strehlow, AT Bäumer, S Baudler, S Wassmann, H Sauer, M Böhm
British Journal of Pharmacology 2000
Plastic Surgical Perspectives on Vascular Endothelial Growth Factor as Gene Therapy for Angiogenesis
PJ Taub, L Silver, H Weinberg
Plastic & Reconstructive Surgery 2000
Decreased urinary excretion of vascular endothelial growth factor in idiopathic membranous glomerulonephritis
EO Honkanen, AM Teppo, C Gronhagen-Riska
Kidney International 2000
Laminin acts via beta 1 integrin signalling to alter cholinergic regulation of L-type Ca(2+) current in cat atrial myocytes
YG Wang, AM Samarel, SL Lipsius
The Journal of Physiology 2000
Angiogenesis in inflammatory joint disease: a target for therapeutic intervention
PE Brenchley
Clinical & Experimental Immunology 2000
Ceramide mimics tumour necrosis factor-α in the induction of cell cycle arrest in endothelial cells
R López-Marure, JL Ventura, L Sánchez, LF Montaño, A Zentella
European Journal of Biochemistry 2000
Endometrial angiogenesis
G Weston, PA Rogers
Best Practice & Research Clinical Obstetrics & Gynaecology 2000
Up-regulation of vascular endothelial growth factor receptor Flt-1 after endothelial denudation: role of transcription factor Egr-1
F Vidal, J Aragonés, A Alfranca, MO de Landázuri
Blood 2000
Doxorubicin Represses CARP Gene Transcription Through the Generation of Oxidative Stress in Neonatal Rat Cardiac Myocytes: Possible Role of Serine/Threonine Kinase-dependent Pathways
Y Aihara, M Kurabayashi, T Tanaka, S Takeda, K Tomaru, K Sekiguchi, Y Ohyama, R Nagai
Journal of Molecular and Cellular Cardiology 2000
The human herpesvirus 8 homolog of Epstein-Barr virus SM protein (KS-SM) is a posttranscriptional activator of gene expression
AK Gupta, V Ruvolo, C Patterson, S Swaminathan
Journal of virology 2000
Laminin binding to beta1-integrins selectively alters beta1- and beta2-adrenoceptor signalling in cat atrial myocytes
YG Wang, AM Samarel, SL Lipsius
The Journal of Physiology 2000
Nosocomial Pneumonia
UL Specks
Nosocomial Pneumonia 2000
Homeostatic Modulation of Cell Surface KDR and Flt1 Expression and Expression of the Vascular Endothelial Cell Growth Factor (VEGF) Receptor mRNAs by VEGF
D Wang, DB Donner, RS Warren
The Journal of biological chemistry 2000
Expression of Vascular Endothelial Growth Factor Receptors in the Human Endometrium: Modulation During the Menstrual Cycle1
G Meduri, P Bausero, M Perrot-Applanat
Biology of reproduction 2000
Tumor Necrosis Factor Employs a Protein-tyrosine Phosphatase to Inhibit Activation of KDR and Vascular Endothelial Cell Growth Factor-induced Endothelial Cell Proliferation
DQ Guo, LW Wu, JD Dunbar, ON Ozes, LD Mayo, KM Kessler, JA Gustin, MR Baerwald, EA Jaffe, RS Warren, DB Donner
The Journal of biological chemistry 2000
Vascular Endothelial Growth Factor KDR Receptor Signaling Potentiates Tumor Necrosis Factor-induced Tissue Factor Expression in Endothelial Cells
BQ Shen, DY Lee, KM Cortopassi, LA Damico, TF Zioncheck
The Journal of biological chemistry 2000
Increasing endothelial cell specific expression by the use of heterologous hypoxic and cytokine-inducible enhancers
U Modlich, CW Pugh, R Bicknell
Gene Therapy 2000
Role of vascular endothelial growth factor in the regulation of angiogenesis
N Ferrara
Kidney International 1999
Vascular Endothelial Growth Factor (VEGF) and Microvessel Density in Squamous Cell Carcinomas of the Larynx: an Immunohistochemical Study
C Neuchrist
Acta Oto-laryngologica 1999
Stimulation of a vascular smooth muscle cell NAD(P)H oxidase by thrombin. Evidence that p47(phox) may participate in forming this oxidase in vitro and in vivo
C Patterson, J Ruef, NR Madamanchi, P Barry-Lane, Z Hu, C Horaist, CA Ballinger, AR Brasier, C Bode, MS Runge
The Journal of biological chemistry 1999
Tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta down-regulate intercellular adhesion molecule (ICAM)-2 expression on the endothelium
F McLaughlin, B P Hayes, C M Horgan, J E Beesley, C J Campbell, A M Randi
Cell Communication and Adhesion 1999
On the Mechanism of Thrombin-induced Angiogenesis: POTENTIATION OF VASCULAR ENDOTHELIAL GROWTH FACTOR ACTIVITY ON ENDOTHELIAL CELLS BY UP-REGULATION OF ITS RECEPTORS
NE Tsopanoglou, ME Maragoudakis
The Journal of biological chemistry 1999
The Human KDR/flk-1 Gene Contains a Functional Initiator Element That Is Bound and Transactivated by TFII-I
Y Wu, C Patterson
The Journal of biological chemistry 1999
Vascular Growth Factors and Angiogenesis
L Claesson-Welsh
1999
Inflammatory Cytokines and Vascular Endothelial Growth Factor Stimulate the Release of Soluble Tie Receptor From Human Endothelial Cells Via Metalloprotease Activation
R Yabkowitz, S Meyer, T Black, G Elliott, LA Merewether, HK Yamane
Blood 1999
Inhibition of Src Family Kinases by a Combinatorial Action of 5′-AMP and Small Heat Shock Proteins, Identified from the Adult Heart
VS Kasi, D Kuppuswamy
Molecular and cellular biology 1999
The biochemical and physiological characteristics of receptors
EP Feener, GL King
Advanced Drug Delivery Reviews 1998
Pulse treatment of human vascular endothelial cells with high doses of tumor necrosis factor and interferon-gamma results in simultaneous synergistic and reversible effects on proliferation and morphology
A Yilmaz, G Bieler, O Spertini, FJ Lejeune, C Rüegg
International Journal of Cancer 1998
Genomic structure of the human KDR/flk-1 gene
LY Yin, Y Wu, CA Ballinger, C Patterson
Mammalian Genome 1998
Vascular endothelial growth factor
I Zachary
The International Journal of Biochemistry & Cell Biology 1998
Advances in Organ Biology
AJ Liedtke
Advances in Organ Biology 1998
Angiotensin II potentiates vascular endothelial growth factor-induced angiogenic activity in retinal microcapillary endothelial cells
A Otani, H Takagi, K Suzuma, Y Honda
Circulation research 1998
Proinflammatory cytokines regulate expression of the lymphatic endothelial mitogen vascular endothelial growth factor-C
A Ristimäki, K Narko, B Enholm, V Joukov, K Alitalo
The Journal of biological chemistry 1998
Transcription factors Sp1 and Sp3 alter vascular endothelial growth factor receptor expression through a novel recognition sequence
Y Hata, E Duh, K Zhang, GS Robinson, LP Aiello
The Journal of biological chemistry 1998
Increased Vascular Endothelial Growth Factor Production in the Lungs of Rats with Hypoxia-induced Pulmonary Hypertension
H Christou, A Yoshida, V Arthur, T Morita, S Kourembanas
American journal of respiratory cell and molecular biology 1998
Regulation of Vascular Endothelial Growth Factor Receptor-2 (Flk-1) Expression in Vascular Endothelial Cells
MS Pepper, SJ Mandriota
Experimental Cell Research 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
E Giraudo, L Primo, E Audero, HP Gerber, P Koolwijk, S Soker, M Klagsbrun, N Ferrara, F Bussolino
The Journal of biological chemistry 1998
Effect of TNF-α on SMIT mRNA levels and myo -inositol accumulation in cultured endothelial cells
MA Yorek, JA Dunlap, MJ Thomas, PR Cammarata, C Zhou, WL Lowe
American journal of physiology. Cell physiology 1998
Restoration of E2F Expression Rescues Vascular Endothelial Cells From Tumor Necrosis Factor- Induced Apoptosis
I Spyridopoulos, N Principe, KL Krasinski, S Xu, M Kearney, M Magner, JM Isner, DW Losordo
Circulation 1998
Genomic structure of the human KDR/flk-1 gene.
Yin LY, Wu Y, Ballinger CA, Patterson C
Mammalian genome : official journal of the International Mammalian Genome Society 1998
Arterial Wall Neovascularization
K Pels, M Labinaz, ER O'Brien
Japanese Circulation Journal 1997
Halting angiogenesis suppresses carcinoma cell invasion
M Skobe, P Rockwell, N Goldstein, S Vosseler, NE Fusenig
Nature Medicine 1997
Interference with c-myc Expression and RB Phosphorylation during TNF-Mediated Growth Arrest in Human Endothelial Cells
R López-Marure, AE Bernal, A Zentella
Biochemical and Biophysical Research Communications 1997
Side effects of cancer treatment with recombinant human tumour necrosis factor alpha: a new challenge for the intensive care unit
JH Zwaveling, JK Maring, AR Giribes, HS Koops
Clinical Intensive Care 1997
The Biology of Vascular Endothelial Growth Factor
N Ferrara, T Davis-Smyth
Endocrine reviews 1997
The Genetics of Cancer
BA Ponder, MJ Waring
The Genetics of Cancer 1995

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