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Cell Growth & Differentiation, Vol 7, Issue 4 469-480, Copyright © 1996 by American Association of Cancer Research


ARTICLES

A novel transforming growth factor beta response element controls the expression of the connective tissue growth factor gene

GR Grotendorst, H Okochi and N Hayashi
Department of Cell Biology and Anatomy, University of Miami School of Medicine, FL 33136, USA.

We reported previously that transforming growth factor beta (TGF-beta) selectively induced high levels of connective tissue growth factor (CTGF) mRNA and protein in human skin fibroblasts. In this study, we investigated the molecular mechanism for TGF-beta regulation of CTGF gene expression. Northern blot and run-on transcription assays indicate that TGF-beta directly activates transcription of the CTGF gene. Fragments of the 5'flanking region of the human CTGF gene were linked to luciferase reporter constructs. TGF-beta induced a 25-30 fold increase in luciferase activity in NIH/3T3 fibroblasts that had been transfected with this construct compared with nontreated cells after 24 h incubation. Other growth factors, such as platelet derived growth factor or fibroblast growth factor, caused only a 2-3-fold induction. This response to TGF-beta occurred only in human skin fibroblasts, fetal bovine aortic smooth muscle cells, and NIH/3T3 fibroblasts but not in the epithelial cell lines tested. Analysis of deletion mutants indicated that an important TGF-beta regulatory element is located between positions -162 and -128 of the CTGF promoter sequence. A fragment of the promoter containing this region conferred TGF-beta induction to a SV40 enhanceriess promoter. Methylation interference and competition gel shift assays mapped a unique 13-nucleotide sequence delineating a novel TGF-beta cis-regulatory element. Point mutations in this region result in a complete loss of the TGF-beta induction, identifying this sequence as a new TGF-beta response element.


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J Biol ChemHome page
R. C. Chambers, P. Leoni, O. P. Blanc-Brude, D. E. Wembridge, and G. J. Laurent
Thrombin Is a Potent Inducer of Connective Tissue Growth Factor Production via Proteolytic Activation of Protease-activated Receptor-1
J. Biol. Chem., November 10, 2000; 275(45): 35584 - 35591.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Endocrinol. Metab.Home page
R. C. Pereira, D. Durant, and E. Canalis
Transcriptional regulation of connective tissue growth factor by cortisol in osteoblasts
Am J Physiol Endocrinol Metab, September 1, 2000; 279(3): E570 - E576.
[Abstract] [Full Text] [PDF]


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J Biol ChemHome page
D. J. Abraham, X. Shiwen, C. M. Black, S. Sa, Y. Xu, and A. Leask
Tumor Necrosis Factor {alpha} Suppresses the Induction of Connective Tissue Growth Factor by Transforming Growth Factor-{beta} in Normal and Scleroderma Fibroblasts
J. Biol. Chem., May 19, 2000; 275(20): 15220 - 15225.
[Abstract] [Full Text] [PDF]


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IOVSHome page
M. F. Cordeiro, S. S. Bhattacharya, G. S. Schultz, and P. T. Khaw
TGF-{beta}1, -{beta}2, and -{beta}3 In Vitro: Biphasic Effects on Tenon’s Fibroblast Contraction, Proliferation, and Migration
, March 1, 2000; 41(3): 756 - 763.
[Abstract] [Full Text]


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Genes Dev.Home page
L. Xu, R. B. Corcoran, J. W. Welsh, D. Pennica, and A. J. Levine
WISP-1 is a Wnt-1- and beta -catenin-responsive oncogene
Genes & Dev., March 1, 2000; 14(5): 585 - 595.
[Abstract] [Full Text]


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J. Am. Soc. Nephrol.Home page
B. L. RISER, M. DENICHILO, P. CORTES, C. BAKER, J. M. GRONDIN, J. YEE, and R. G. NARINS
Regulation of Connective Tissue Growth Factor Activity in Cultured Rat Mesangial Cells and Its Expression in Experimental Diabetic Glomerulosclerosis
J. Am. Soc. Nephrol., January 1, 2000; 11(1): 25 - 38.
[Abstract] [Full Text]


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J Biol ChemHome page
K. Hishikawa, B. S. Oemar, F. C. Tanner, T. Nakaki, T. F. Luscher, and T. Fujii
Connective Tissue Growth Factor Induces Apoptosis in Human Breast Cancer Cell Line MCF-7
J. Biol. Chem., December 24, 1999; 274(52): 37461 - 37466.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
D. A. Ricupero, D. C. Rishikof, P.-P. Kuang, C. F. Poliks, and R. H. Goldstein
Regulation of connective tissue growth factor expression by prostaglandin E2
Am J Physiol Lung Cell Mol Physiol, December 1, 1999; 277(6): L1165 - L1171.
[Abstract] [Full Text] [PDF]


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CirculationHome page
K. Hishikawa, B. S. Oemar, F. C. Tanner, T. Nakaki, T. Fujii, and T. F. Luscher
Overexpression of Connective Tissue Growth Factor Gene Induces Apoptosis in Human Aortic Smooth Muscle Cells
Circulation, November 16, 1999; 100(20): 2108 - 2112.
[Abstract] [Full Text] [PDF]


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IOVSHome page
M. F. Cordeiro, J. A. Gay, and P. T. Khaw
Human Anti-Transforming Growth Factor-{beta}2 Antibody: A New Glaucoma Anti-Scarring Agent
, September 1, 1999; 40(10): 2225 - 2234.
[Abstract] [Full Text] [PDF]


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IOVSHome page
E. H. Lee and C.-K. Joo
Role of Transforming Growth Factor-{beta} in Transdifferentiation and Fibrosis of Lens Epithelial Cells
, August 1, 1999; 40(9): 2025 - 2032.
[Abstract] [Full Text] [PDF]


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Mol. Cell. Biol.Home page
A. M. Babic, C.-C. Chen, and L. F. Lau
Fisp12/Mouse Connective Tissue Growth Factor Mediates Endothelial Cell Adhesion and Migration through Integrin alpha vbeta 3, Promotes Endothelial Cell Survival, and Induces Angiogenesis In Vivo
Mol. Cell. Biol., April 1, 1999; 19(4): 2958 - 2966.
[Abstract] [Full Text] [PDF]


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Biol. Reprod.Home page
G. A. Surveyor, A. K. Wilson, and D. R. Brigstock
Localization of Connective Tissue Growth Factor during the Period of Embryo Implantation in the Mouse
Biol Reprod, November 1, 1998; 59(5): 1207 - 1213.
[Abstract] [Full Text]


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Biol. Reprod.Home page
D. K. Ball,, G. A. Surveyor,, J. R. Diehl,, C. L. Steffen,, M. Uzumcu,, M. A. Mirando,, and D. R. Brigstock
Characterization of 16- to 20-Kilodalton (kDa) Connective Tissue Growth Factors (CTGFs) and Demonstration of Proteolytic Activity for 38-kDa CTGF in Pig Uterine Luminal Flushings
Biol Reprod, October 1, 1998; 59(4): 828 - 835.
[Abstract] [Full Text]


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FASEB J.Home page
D. Kothapalli, N. Hayashi, and G. R. Grotendorst
Inhibition of TGF-ß-stimulated CTGF gene expression and anchorage-independent growth by cAMP identifies a CTGF-dependent restriction point in the cell cycle
FASEB J, September 1, 1998; 12(12): 1151 - 1161.
[Abstract] [Full Text]


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Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J. A. Lasky, L. A. Ortiz, B. Tonthat, G. W. Hoyle, M. Corti, G. Athas, G. Lungarella, A. Brody, and M. Friedman
Connective tissue growth factor mRNA expression is upregulated in bleomycin-induced lung fibrosis
Am J Physiol Lung Cell Mol Physiol, August 1, 1998; 275(2): L365 - L371.
[Abstract] [Full Text] [PDF]


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J Biol ChemHome page
J. Dammeier, H.-D. Beer, M. Brauchle, and S. Werner
Dexamethasone Is a Novel Potent Inducer of Connective Tissue Growth Factor Expression: IMPLICATIONS FOR GLUCOCORTICOID THERAPY
J. Biol. Chem., July 17, 1998; 273(29): 18185 - 18190.
[Abstract] [Full Text] [PDF]


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J Biol ChemHome page
D. R. Brigstock, C. L. Steffen, G. Y. Kim, R. K. Vegunta, J. R. Diehl, and P. A. Harding
Purification and Characterization of Novel Heparin-binding Growth Factors in Uterine Secretory Fluids: IDENTIFICATION AS HEPARIN-REGULATED M r10,000 FORMS OF CONNECTIVE TISSUE GROWTH FACTOR
J. Biol. Chem., August 8, 1997; 272(32): 20275 - 20282.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
B. S. Oemar and T. F. Luscher
Connective Tissue Growth Factor : Friend or Foe?
Arterioscler Thromb Vasc Biol, August 1, 1997; 17(8): 1483 - 1489.
[Abstract] [Full Text]


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J Biol ChemHome page
A. Hahn, J. Heusinger-Ribeiro, T. Lanz, S. Zenkel, and M. Goppelt-Struebe
Induction of Connective Tissue Growth Factor by Activation of Heptahelical Receptors: MODULATION BY Rho PROTEINS AND THE ACTIN CYTOSKELETON
J. Biol. Chem., December 1, 2000; 275(48): 37429 - 37435.
[Abstract] [Full Text] [PDF]


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J Biol ChemHome page
R. C. Chambers, P. Leoni, O. P. Blanc-Brude, D. E. Wembridge, and G. J. Laurent
Thrombin Is a Potent Inducer of Connective Tissue Growth Factor Production via Proteolytic Activation of Protease-activated Receptor-1
J. Biol. Chem., November 10, 2000; 275(45): 35584 - 35591.
[Abstract] [Full Text] [PDF]


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J Biol ChemHome page
K. Suzuma, K. Naruse, I. Suzuma, N. Takahara, K. Ueki, L. P. Aiello, and G. L. King
Vascular Endothelial Growth Factor Induces Expression of Connective Tissue Growth Factor via KDR, Flt1, and Phosphatidylinositol 3-Kinase-Akt-dependent Pathways in Retinal Vascular Cells
J. Biol. Chem., December 29, 2000; 275(52): 40725 - 40731.
[Abstract] [Full Text] [PDF]


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J Biol ChemHome page
A. Holmes, D. J. Abraham, S. Sa, X. Shiwen, C. M. Black, and A. Leask
CTGF and SMADs, Maintenance of Scleroderma Phenotype Is Independent of SMAD Signaling
J. Biol. Chem., April 6, 2001; 276(14): 10594 - 10601.
[Abstract] [Full Text] [PDF]


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J Biol ChemHome page
K. Hishikawa, B. S. Oemar, and T. Nakaki
Static Pressure Regulates Connective Tissue Growth Factor Expression in Human Mesangial Cells
J. Biol. Chem., May 18, 2001; 276(20): 16797 - 16803.
[Abstract] [Full Text] [PDF]


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J Biol ChemHome page
P. R. Segarini, J. E. Nesbitt, D. Li, L. G. Hays, J. R. Yates III, and D. F. Carmichael
The Low Density Lipoprotein Receptor-related Protein/{alpha}2-Macroglobulin Receptor Is a Receptor for Connective Tissue Growth Factor
J. Biol. Chem., November 2, 2001; 276(44): 40659 - 40667.
[Abstract] [Full Text] [PDF]




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