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Science 8 March 1996:
Vol. 271. no. 5254, pp. 1427 - 1431
DOI: 10.1126/science.271.5254.1427
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Reports

Egr-1-Induced Endothelial Gene Expression: A Common Theme in Vascular Injury

Levon M. Khachigian, * Volkhard Lindner, dagger Amy J. Williams, Tucker Collins ddagger

A number of pathophysiologically relevant genes, including platelet-derived growth factor B-chain (PDGF-B), are induced in the vasculature after acute mechanical injury. In rat aorta, the activated expression of these genes was preceded by a marked increase in the amount of the early-growth-response gene product Egr-1 at the endothelial wound edge. Egr-1 interacts with a novel element in the proximal PDGF-B promoter, as well as with consensus elements in the promoters of other genes induced by endothelial injury. This interaction is crucial for injury-induced PDGF-B promoter-dependent expression. Sp1, whose binding site in the PDGF-B promoter overlaps that of Egr-1, occupies this element in unstimulated cells and is displaced by increasing amounts of Egr-1. These findings implicate Egr-1 in the up-regulated expression of PDGF-B and other potent mediators in mechanically injured arterial endothelial cells.

L. M. Khachigian, A. J. Williams, T. Collins, Vascular Research Division, Department of Pathology, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA 02115, USA.
V. Lindner, Department of Pathology, University of Washington, Seattle, WA 98195, USA.
* Present address: Centre for Thrombosis and Vascular Research, School of Pathology, University of New South Wales, Sydney, NSW 2052, Australia.
dagger Present address: Department of Surgery, Maine Medical Center Research Institute, South Portland, ME 04106, USA.
ddagger To whom correspondence should be addressed.


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   Abstract »    Full Text »    PDF »
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E. V. Gerasimovskaya, S. Ahmad, C. W. White, P. L. Jones, T. C. Carpenter, and K. R. Stenmark (2002)
J. Biol. Chem. 277, 44638-44650
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Transcription Factor Sp1 Phosphorylation Induced by Shear Stress Inhibits Membrane Type 1-Matrix Metalloproteinase Expression in Endothelium.
S. Yun, A. Dardik, M. Haga, A. Yamashita, S. Yamaguchi, Y. Koh, J. A. Madri, and B. E. Sumpio (2002)
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Transcriptional Control of Cardiac Allograft Vasculopathy by Early Growth Response Gene-1 (Egr-1).
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Transactivation via RAR/RXR-Sp1 Interaction: Characterization of Binding Between Sp1 and GC Box Motif.
J. Shimada, Y. Suzuki, S.-J. Kim, P.-C. Wang, M. Matsumura, and S. Kojima (2001)
Mol. Endocrinol. 15, 1677-1692
   Abstract »    Full Text »    PDF »
Lysophosphatidylcholine Induces Early Growth Response Factor-1 Expression and Activates the Core Promoter of PDGF-A Chain in Vascular Endothelial Cells.
M. Morimoto, N. Kume, S. Miyamoto, Y. Ueno, H. Kataoka, M. Minami, K. Hayashida, N. Hashimoto, and T. Kita (2001)
Arterioscler Thromb Vasc Biol 21, 771-776
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Hypoxia Activates Jun-N-Terminal Kinase, Extracellular Signal-Regulated Protein Kinase, and p38 Kinase in Pulmonary Arteries.
N. Jin, N. Hatton, D. R. Swartz, X.-l. Xia, M. A. Harrington, S. H. Larsen, and R. A. Rhoades (2000)
Am. J. Respir. Cell Mol. Biol. 23, 593-601
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The Egr-1 gene is induced by epidermal growth factor in ECV304 cells and primary endothelial cells.
J. C. Tsai, L. Liu, J. Guan, and W. C. Aird (2000)
Am J Physiol Cell Physiol 279, C1414-C1424
   Abstract »    Full Text »    PDF »
Expression of Egr-1 in Late Stage Emphysema.
W. Zhang, S. D. Yan, A. Zhu, Y. S. Zou, M. Williams, G. C. Godman, B. M. Thomashow, M. E. Ginsburg, D. M. Stern, and S.-F. Yan (2000)
Am. J. Pathol. 157, 1311-1320
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Oxidative stress and expression of p22phox are involved in the up-regulation of tissue factor in vascular smooth muscle cells in response to activated platelets.
A. GÖRLACH, R. P. BRANDES, S. BASSUS, N. KRONEMANN, C. M. KIRCHMAIER, R. BUSSE, and V. B. SCHINI-KERTH (2000)
FASEB J 14, 1518-1528
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Pulmonary expression of early growth response-1: biphasic time course and effect of oxygen concentration.
S.-F. Yan, J. Lu, L. Xu, Y. S. Zou, J. Tongers, W. Kisiel, N. Mackman, D. J. Pinsky, and D. M. Stern (2000)
J Appl Physiol 88, 2303-2309
   Abstract »    Full Text »    PDF »
Up-regulation of vascular endothelial growth factor receptor Flt-1 after endothelial denudation: role of transcription factor Egr-1.
F. Vidal, J. Aragones, A. Alfranca, and M. O. de Landazuri (2000)
Blood 95, 3387-3395
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Induction of Platelet-derived Growth Factor B-chain Expression by Transforming Growth Factor-beta Involves Transactivation by Smads.
L. M. Taylor and L. M. Khachigian (2000)
J. Biol. Chem. 275, 16709-16716
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A Novel Activation Function for NAB Proteins in EGR-dependent Transcription of the Luteinizing Hormone beta Gene.
B. R. Sevetson, J. Svaren, and J. Milbrandt (2000)
J. Biol. Chem. 275, 9749-9757
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Inhibition of the RelA(p65) NF-kappa B Subunit by Egr-1.
N. R. Chapman and N. D. Perkins (2000)
J. Biol. Chem. 275, 4719-4725
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Transcriptional activation of urokinase by the Kruppel-like factor Zf9/COPEB activates latent TGF-beta 1 in vascular endothelial cells.
S. Kojima, S. Hayashi, K. Shimokado, Y. Suzuki, J. Shimada, M. P. Crippa, and S. L. Friedman (2000)
Blood 95, 1309-1316
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Zinc Finger Transcription Factor Egr-1 Activates Flt-1 Gene Expression in THP-1 Cells on Induction for Macrophage Differentiation.
N. Akuzawa, M. Kurabayashi, Y. Ohyama, M. Arai, and R. Nagai (2000)
Arterioscler Thromb Vasc Biol 20, 377-384
   Abstract »    Full Text »    PDF »
Genetic Variations in the 5-Lipoxygenase Core Promoter . Description and Functional Implications.
E. S. SILVERMAN and J. M. DRAZEN (2000)
Am. J. Respir. Crit. Care Med. 161, S77-80
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Transcriptional Activation of the Zinc Finger Transcription Factor BTEB2 Gene by Egr-1 Through Mitogen-Activated Protein Kinase Pathways in Vascular Smooth Muscle Cells.
K. Kawai-Kowase, M. Kurabayashi, Y. Hoshino, Y. Ohyama, and R. Nagai (1999)
Circ. Res. 85, 787-795
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A Mouse Model of Arterial Gene Transfer : Antigen-Specific Immunity Is a Minor Determinant of the Early Loss of Adenovirus-Mediated Transgene Expression.
G. Vassalli, R. Agah, R. Qiao, C. Aguilar, and D. A. Dichek (1999)
Circ. Res. 85 , e25-e32
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Angiotensin II Stimulates Platelet-Derived Growth Factor-B Chain Expression in Newborn Rat Vascular Smooth Muscle Cells and Neointimal Cells Through Ras, Extracellular Signal-Regulated Protein Kinase, and c-Jun N-Terminal Protein Kinase Mechanisms.
J.-o Deguchi, M. Makuuchi, T. Nakaoka, T. Collins, and Y. Takuwa (1999)
Circ. Res. 85, 565-574
   Abstract »    Full Text »    PDF »
NAB2: A Transcriptional Brake for Activated Gene Expression in the Vessel Wall?.
J. M. Miano and B. C. Berk (1999)
Am. J. Pathol. 155, 1009-1012
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Vascular Smooth Muscle Cells Express the Transcriptional Corepressor NAB2 in Response to Injury.
E. S. Silverman, L. M. Khachigian, F. S. Santiago, A. J. Williams, V. Lindner, and T. Collins (1999)
Am. J. Pathol. 155, 1311-1317
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Transcriptional Regulation of the Platelet-derived Growth Factor alpha Receptor Gene via CCAAT/Enhancer-binding Protein-delta in Vascular Smooth Muscle Cells.
T. Fukuoka, Y. Kitami, T. Okura, and K. Hiwada (1999)
J. Biol. Chem. 274, 25576-25582
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Hypoxia/Hypoxemia-Induced Activation of the Procoagulant Pathways and the Pathogenesis of Ischemia-Associated Thrombosis.
S.-F. Yan, N. Mackman, W. Kisiel, D. M. Stern, and D. J. Pinsky (1999)
Arterioscler Thromb Vasc Biol 19, 2029-2035
   Abstract »    Full Text »    PDF »
Vascular Smooth Muscle Cell Proliferation and Regrowth after Mechanical Injury in Vitro Are Egr-1/NGFI-A-Dependent.
F. S. Santiago, D. G. Atkins, and L. M. Khachigian (1999)
Am. J. Pathol. 155, 897-905
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Egr-1 Mediates Extracellular Matrix-driven Transcription of Membrane Type 1 Matrix Metalloproteinase in Endothelium.
T. L. Haas, D. Stitelman, S. J. Davis, S. S. Apte, and J. A. Madri (1999)
J. Biol. Chem. 274, 22679-22685
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Nitric Oxide Regulates Shear Stress–Induced Early Growth Response-1 : Expression via the Extracellular Signal–Regulated Kinase Pathway in Endothelial Cells.
J. J. Chiu, B. S. Wung, H. J. Hsieh, L. W. Lo, and D. L. Wang (1999)
Circ. Res. 85, 238-246
   Abstract »    Full Text »    PDF »


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