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Journal of Cell Science, Vol 108, Issue 3 985-1002, Copyright © 1995 by Company of Biologists


JOURNAL ARTICLES

Neutralisation of TGF-beta 1 and TGF-beta 2 or exogenous addition of TGF-beta 3 to cutaneous rat wounds reduces scarring

M Shah, DM Foreman and MW Ferguson
Cells, Immunology and Development Division, School of Biological Sciences, University of Manchester, UK.

Exogenous addition of neutralising antibody to transforming growth factor-beta 1,2 to cutaneous wounds in adult rodents reduces scarring. Three isoforms of transforming growth factor-beta (1, 2 and 3) have been identified in mammals. We investigated the isoform/isoforms of TGF-beta responsible for cutaneous scarring by: (i) reducing specific endogenous TGF-beta isoforms by exogenous injection of isoform specific neutralising antibodies; and (ii) increasing the level of specific TGF-beta isoforms by exogenous infiltration into the wound margins. Exogenous addition of neutralising antibody to TGF-beta 1 plus neutralising antibody to TGF-beta 2 reduced the monocyte and macrophage profile, neovascularisation, fibronectin, collagen III and collagen I deposition in the early stages of wound healing compared to control wounds. Treatment with neutralising antibodies to TGF-betas 1 and 2 markedly improved the architecture of the neodermis to resemble that of normal dermis and reduced scarring while the control wounds healed with scar formation. Exogenous addition of neutralising antibody to TGF-beta 1 alone also reduced the monocyte and macrophage profile, fibronectin, collagen III and collagen I deposition compared to control wounds. However, treatment with neutralising antibody to TGF-beta 1 alone only marginally reduced scarring. By contrast, wounds treated with neutralising antibody to TGF-beta 2 alone did not differ from control wounds. Interestingly, exogenous addition of the TGF-beta 3 peptide also reduced the monocyte and macrophage profile, fibronectin, collagen I and collagen III deposition in the early stages of wound healing and markedly improved the architecture of the neodermis and reduced scarring. By contrast, wounds treated with either TGF-beta 1 or with TGF-beta 2 had more extracellular matrix deposition in the early stages of wound healing but did not differ from control wounds in the final quality of scarring. This study clearly demonstrates isoform specific differences in the role of TGF-betas in wound healing and cutaneous scarring. TGF-beta 1 and TGF-beta 2 are implicated in cutaneous scarring. This study also suggests a novel therapeutic use of exogenous recombinant, TGF-beta 3 as an anti-scarring agent.
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G. I Mason, J. Hamburger, and J. B Matthews
Mast cells, extracellular matrix components, TGFbeta isoforms and TGFbeta receptor expression in labial salivary glands in systemic sclerosis
Ann Rheum Dis, March 1, 2000; 59(3): 183 - 189.
[Abstract] [Full Text]


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FASEB J.Home page
E. PIEK, C.-H. HELDIN, and P. TEN DIJKE
Specificity, diversity, and regulation in TGF-{beta} superfamily signaling
FASEB J, December 1, 1999; 13(15): 2105 - 2124.
[Abstract] [Full Text]


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J. Biol. Chem.Home page
S. S. Huang, M. Zhou, F. E. Johnson, H.-S. Shieh, and J. S. Huang
An Active Site of Transforming Growth Factor-beta 1 for Growth Inhibition and Stimulation
J. Biol. Chem., September 24, 1999; 274(39): 27754 - 27758.
[Abstract] [Full Text] [PDF]


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NEJMHome page
A. J. Singer and R. A.F. Clark
Cutaneous Wound Healing
N. Engl. J. Med., September 2, 1999; 341(10): 738 - 746.
[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
Invest. Ophthalmol. Vis. Sci., September 1, 1999; 40(10): 2225 - 2234.
[Abstract] [Full Text] [PDF]


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IOVSHome page
J. V. Jester, J. Huang, P. A. Barry-Lane, W. W-Y. Kao, W. M. Petroll, and H. D. Cavanagh
Transforming Growth Factor{beta}-Mediated Corneal Myofibroblast Differentiation Requires Actin and Fibronectin Assembly
Invest. Ophthalmol. Vis. Sci., August 1, 1999; 40(9): 1959 - 1967.
[Abstract] [Full Text] [PDF]


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IOVSHome page
M. F. Cordeiro, M. B. Reichel, J. A. Gay, F. D’Esposita, R. A. Alexander, and P. T. Khaw
Transforming Growth Factor-{beta}1, -{beta}2, and -{beta}3 In Vivo: Effects on Normal and Mitomycin C-Modulated Conjunctival Scarring
Invest. Ophthalmol. Vis. Sci., August 1, 1999; 40(9): 1975 - 1982.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Gastrointest. Liver Physiol.Home page
B. C. McKaig, S. S. Makh, C. J. Hawkey, D. K. Podolsky, and Y. R. Mahida
Normal human colonic subepithelial myofibroblasts enhance epithelial migration (restitution) via TGF-beta 3
Am J Physiol Gastrointest Liver Physiol, May 1, 1999; 276(5): G1087 - G1093.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
J. Li, K. Foitzik, E. Calautti, H. Baden, T. Doetschman, and G. P. Dotto
TGF-beta 3, but Not TGF-beta 1, Protects Keratinocytes against 12-O-Tetradecanoylphorbol-13-acetate-induced Cell Death in Vitro and in Vivo
J. Biol. Chem., February 12, 1999; 274(7): 4213 - 4219.
[Abstract] [Full Text] [PDF]


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Br J OphthalmolHome page
M F CORDEIRO and P T KHAW
The healing optic nerve in glaucoma: transforming growth factor beta  and optic nerve head remodelling
Br J Ophthalmol, February 1, 1999; 83(2): 132 - 133.
[Full Text]


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DevelopmentHome page
Y Taya, S O'Kane, and M. Ferguson
Pathogenesis of cleft palate in TGF-beta3 knockout mice
Development, January 9, 1999; 126(17): 3869 - 3879.
[Abstract] [PDF]


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Am. J. Pathol.Home page
L. Yang, C. X. Qiu, A. Ludlow, M. W. J. Ferguson, and G. Brunner
Active Transforming Growth Factor-ß in Wound Repair : Determination Using a New Assay
Am. J. Pathol., January 1, 1999; 154(1): 105 - 111.
[Abstract] [Full Text] [PDF]


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Am. J. Pathol.Home page
J. Wang, H. Zheng, C.-C. Sung, K. K. Richter, and M. Hauer-Jensen
Cellular Sources of Transforming Growth Factor-ß Isoforms in Early and Chronic Radiation Enteropathy
Am. J. Pathol., November 1, 1998; 153(5): 1531 - 1540.
[Abstract] [Full Text] [PDF]


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Br J OphthalmolHome page
M. B Reichel, M F. Cordeiro, R. A Alexander, I. A Cree, S. S Bhattacharya, and P. T Khaw
New model of conjunctival scarring in the mouse eye
Br J Ophthalmol, September 1, 1998; 82(9): 1072 - 1077.
[Abstract] [Full Text]


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Br J OphthalmolHome page
Y. KAJI, T. MITA, H. OBATA, T. TSURU, K. SOYA, E. SHIRASAWA, H. SAKAI, A. HANYU, M. KATO, and H. YAMASHITA
Expression of transforming growth factor beta  superfamily and their receptors in the corneal stromal wound healing process after excimer laser keratectomy
Br J Ophthalmol, April 1, 1998; 82(4): 456g - 456.
[Full Text]


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Arterioscler. Thromb. Vasc. Bio.Home page
M. R. Ward, A. Agrotis, P. Kanellakis, R. Dilley, G. Jennings, and A. Bobik
Inhibition of Protein Tyrosine Kinases Attenuates Increases in Expression of Transforming Growth Factor-ß Isoforms and Their Receptors Following Arterial Injury
Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 2461 - 2470.
[Abstract] [Full Text]


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J. Biol. Chem.Home page
S. S. Huang, Q. Liu, F. E. Johnson, Y. Konish, and J. S. Huang
Transforming Growth Factor beta  Peptide Antagonists and Their Conversion to Partial Agonists
J. Biol. Chem., October 24, 1997; 272(43): 27155 - 27159.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
Q. Liu, S. S. Huang, and J. S. Huang
Function of the Type V Transforming Growth Factor beta  Receptor in Transforming Growth Factor beta -induced Growth Inhibition of Mink Lung Epithelial Cells
J. Biol. Chem., July 25, 1997; 272(30): 18891 - 18895.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
M. Lyon, G. Rushton, and J. T. Gallagher
The Interaction of the Transforming Growth Factor-beta s with Heparin/Heparan Sulfate Is Isoform-specific
J. Biol. Chem., July 18, 1997; 272(29): 18000 - 18006.
[Abstract] [Full Text] [PDF]


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Arch SurgHome page
L. Wu, A. Siddiqui, D. E. Morris, D. A. Cox, S. I. Roth, and T. A. Mustoe
Transforming Growth Factor {beta}3 (TGF{beta}3) Accelerates Wound Healing Without Alteration of Scar Prominence: Histologic and Competitive Reverse-Transcription-Polymerase Chain Reaction Studies
Arch Surg, July 1, 1997; 132(7): 753 - 760.
[Abstract] [PDF]


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J. Biol. Chem.Home page
S. Frank, M. Madlener, and S. Werner
Transforming Growth Factors beta1, beta2, and beta3 and Their Receptors Are Differentially Regulated during Normal and Impaired Wound Healing
J. Biol. Chem., April 26, 1996; 271(17): 10188 - 10193.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Cell Physiol.Home page
B. C. McKaig, K. Hughes, P. J. Tighe, and Y. R. Mahida
Differential expression of TGF-beta isoforms by normal and inflammatory bowel disease intestinal myofibroblasts
Am J Physiol Cell Physiol, January 1, 2002; 282(1): C172 - C182.
[Abstract] [Full Text] [PDF]




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