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

Mouza T. Goova, Jun Li, Thomas Kislinger, Wu Qu, Yan Lu, Loredana G. Bucciarelli, Sarah Nowygrod, Bonnie M. Wolf, Xzabia Caliste, Shi Fang Yan, David Stern, Ann Marie Schmidt

Research output: Contribution to journalArticle

313 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)513-525
Number of pages13
JournalAmerican Journal of Pathology
Volume159
Issue number2
DOIs
StatePublished - Jan 1 2001

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Wound Healing
Wounds and Injuries
Leukocyte L1 Antigen Complex
Proto-Oncogene Proteins c-sis
Cytokines
Ligands
Matrix Metalloproteinase 3
Granulation Tissue
Matrix Metalloproteinase 2
Vascular Endothelial Growth Factor A
Interleukin-6
Tumor Necrosis Factor-alpha
Advanced Glycosylation End Product-Specific Receptor

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Goova, M. T., Li, J., Kislinger, T., Qu, W., Lu, Y., Bucciarelli, L. G., ... Schmidt, A. M. (2001). Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice. American Journal of Pathology, 159(2), 513-525. https://doi.org/10.1016/S0002-9440(10)61723-3

Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice. / Goova, Mouza T.; Li, Jun; Kislinger, Thomas; Qu, Wu; Lu, Yan; Bucciarelli, Loredana G.; Nowygrod, Sarah; Wolf, Bonnie M.; Caliste, Xzabia; Yan, Shi Fang; Stern, David; Schmidt, Ann Marie.

In: American Journal of Pathology, Vol. 159, No. 2, 01.01.2001, p. 513-525.

Research output: Contribution to journalArticle

Goova, MT, Li, J, Kislinger, T, Qu, W, Lu, Y, Bucciarelli, LG, Nowygrod, S, Wolf, BM, Caliste, X, Yan, SF, Stern, D & Schmidt, AM 2001, 'Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice', American Journal of Pathology, vol. 159, no. 2, pp. 513-525. https://doi.org/10.1016/S0002-9440(10)61723-3
Goova, Mouza T. ; Li, Jun ; Kislinger, Thomas ; Qu, Wu ; Lu, Yan ; Bucciarelli, Loredana G. ; Nowygrod, Sarah ; Wolf, Bonnie M. ; Caliste, Xzabia ; Yan, Shi Fang ; Stern, David ; Schmidt, Ann Marie. / Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice. In: American Journal of Pathology. 2001 ; Vol. 159, No. 2. pp. 513-525.
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