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From the Departments of Surgery,
*
Medicine,
and Physiology and Cellular
Biophysics,
College of Physicians &
Surgeons, Columbia University, New York, New York
Receptor for advanced glycation end-products (RAGE),
and two of its ligands, AGE and EN-RAGEs (members of the
S100/calgranulin family of pro-inflammatory cytokines), display
enhanced expression in slowly resolving full-thickness excisional
wounds developed in genetically diabetic db+/db+ mice. We tested the
concept that blockade of RAGE, using soluble(s) RAGE,
the extracellular ligand-binding domain of the receptor, would
enhance wound closure in these animals. Administration of sRAGE
accelerated the development of appropriately limited inflammatory cell
infiltration and activation in wound foci. In parallel with accelerated
wound closure at later times, blockade of RAGE suppressed
levels of cytokines; tumor necrosis factor-
; interleukin-6; and
matrix metalloproteinases-2, -3, and -9. In
addition, generation of thick, well-vascularized
granulation tissue was enhanced, in parallel with increased
levels of platelet-derived growth factor-B and vascular endothelial
growth factor. These findings identify a central role for RAGE in
disordered wound healing associated with diabetes, and suggest
that blockade of this receptor might represent a targeted strategy to
restore effective wound repair in this disorder.
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A. W. Stitt, C. McGoldrick, A. Rice-McCaldin, D. R. McCance, J. V. Glenn, D. K. Hsu, F.-T. Liu, S. R. Thorpe, and T. A. Gardiner Impaired Retinal Angiogenesis in Diabetes: Role of Advanced Glycation End Products and Galectin-3 Diabetes, March 1, 2005; 54(3): 785 - 794. [Abstract] [Full Text] [PDF]
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Y. Shi, B. Reitmaier, J. Regenbogen, R. M. Slowey, S. R. Opalenik, E. Wolf, A. Goppelt, and J. M. Davidson CARP, a Cardiac Ankyrin Repeat Protein, Is Up-Regulated during Wound Healing and Induces Angiogenesis in Experimental Granulation Tissue Am. J. Pathol., January 1, 2005; 166(1): 303 - 312. [Abstract] [Full Text] [PDF]
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L. L. RONG, W. TROJABORG, W. QU, K. KOSTOV, S. D. YAN, C. GOOCH, M. SZABOLCS, A. P. HAYS, and A. M. SCHMIDT Antagonism of RAGE suppresses peripheral nerve regeneration FASEB J, December 1, 2004; 18(15): 1812 - 1817. [Abstract] [Full Text] [PDF]
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L. E. Hanford, J. J. Enghild, Z. Valnickova, S. V. Petersen, L. M. Schaefer, T. M. Schaefer, T. A. Reinhart, and T. D. Oury Purification and Characterization of Mouse Soluble Receptor for Advanced Glycation End Products (sRAGE) J. Biol. Chem., November 26, 2004; 279(48): 50019 - 50024. [Abstract] [Full Text] [PDF]
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 K. A. Howes, Y. Liu, J. L. Dunaief, A. Milam, J. M. Frederick, A. Marks, and W. Baehr Receptor for Advanced Glycation End Products and Age-Related Macular Degeneration Invest. Ophthalmol. Vis. Sci., October 1, 2004; 45(10): 3713 - 3720. [Abstract] [Full Text] [PDF]
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 I. A. Clark, L. M. Alleva, A. C. Mills, and W. B. Cowden Pathogenesis of Malaria and Clinically Similar Conditions Clin. Microbiol. Rev., July 1, 2004; 17(3): 509 - 539. [Abstract] [Full Text] [PDF]
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 R. Liu, T. Desta, H. He, and D. T. Graves Diabetes Alters the Response to Bacteria by Enhancing Fibroblast Apoptosis Endocrinology, June 1, 2004; 145(6): 2997 - 3003. [Abstract] [Full Text] [PDF]
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R. D. Galiano, O. M. Tepper, C. R. Pelo, K. A. Bhatt, M. Callaghan, N. Bastidas, S. Bunting, H. G. Steinmetz, and G. C. Gurtner Topical Vascular Endothelial Growth Factor Accelerates Diabetic Wound Healing through Increased Angiogenesis and by Mobilizing and Recruiting Bone Marrow-Derived Cells Am. J. Pathol., June 1, 2004; 164(6): 1935 - 1947. [Abstract] [Full Text] [PDF]
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 S.-F. Yan, R. Ramasamy, L. G Bucciarelli, T. Wendt, L. K Lee, B. I Hudson, D. M Stenr, E. Lalla, S. Du Yan, L. L. Rong, et al. RAGE and its ligands: a lasting memory in diabetic complications? Diabetes and Vascular Disease Research, May 1, 2004; 1(1): 10 - 20. [Abstract] [PDF]
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H. He, R. Liu, T. Desta, C. Leone, L. C. Gerstenfeld, and D. T. Graves Diabetes Causes Decreased Osteoclastogenesis, Reduced Bone Formation, and Enhanced Apoptosis of Osteoblastic Cells in Bacteria Stimulated Bone Loss Endocrinology, January 1, 2004; 145(1): 447 - 452. [Abstract] [Full Text] [PDF]
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 S. F. Yan, R. Ramasamy, Y. Naka, and A. M. Schmidt Glycation, Inflammation, and RAGE: A Scaffold for the Macrovascular Complications of Diabetes and Beyond Circ. Res., December 12, 2003; 93(12): 1159 - 1169. [Abstract] [Full Text] [PDF]
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 T. Chavakis, A. Bierhaus, N. Al-Fakhri, D. Schneider, S. Witte, T. Linn, M. Nagashima, J. Morser, B. Arnold, K. T. Preissner, et al. The Pattern Recognition Receptor (RAGE) Is a Counterreceptor for Leukocyte Integrins: A Novel Pathway for Inflammatory Cell Recruitment J. Exp. Med., November 17, 2003; 198(10): 1507 - 1515. [Abstract] [Full Text] [PDF]
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M. Peppa, H. Brem, P. Ehrlich, J.-G. Zhang, W. Cai, Z. Li, A. Croitoru, S. Thung, and H. Vlassara Adverse Effects of Dietary Glycotoxins on Wound Healing in Genetically Diabetic Mice Diabetes, November 1, 2003; 52(11): 2805 - 2813. [Abstract] [Full Text] [PDF]
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 D Foell, S Seeliger, T Vogl, H-G Koch, H Maschek, E Harms, C Sorg, and J Roth Expression of S100A12 (EN-RAGE) in cystic fibrosis Thorax, July 1, 2003; 58(7): 613 - 617. [Abstract] [Full Text] [PDF]
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D. A. Kass Getting Better Without AGE: New Insights Into the Diabetic Heart Circ. Res., April 18, 2003; 92(7): 704 - 706. [Full Text] [PDF]
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O. Z. Lerman, R. D. Galiano, M. Armour, J. P. Levine, and G. C. Gurtner Cellular Dysfunction in the Diabetic Fibroblast: Impairment in Migration, Vascular Endothelial Growth Factor Production, and Response to Hypoxia Am. J. Pathol., January 1, 2003; 162(1): 303 - 312. [Abstract] [Full Text] [PDF]
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G. F. Pierce Inflammation in Nonhealing Diabetic Wounds : The Space-Time Continuum Does Matter Am. J. Pathol., August 1, 2001; 159(2): 399 - 403. [Full Text]
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