Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice / M. Goova, J. Li, T. Kislinger, W. Qu, Y. Lu, L. Bucciarelli, S. Nowygrod, B. Wolf, X. Caliste, S. Yan, D. Stern, A. Schmidt. - In: THE AMERICAN JOURNAL OF PATHOLOGY. - ISSN 0002-9440. - 169:2(2001 Aug), pp. 513-525. [10.1016/S0002-9440(10)61723-3]

Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice

L. Bucciarelli;
2001

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-α; 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.
Settore MED/13 - Endocrinologia
ago-2001
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1045752
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