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ACS Chem Biol. 2014 Jan 17;9(1):105-10. doi: 10.1021/cb4005468. Epub 2013 Sep 26.

A chemical biological strategy to facilitate diabetic wound healing.

Author information

1
Department of Chemistry and Biochemistry, University of Notre Dame , Notre Dame, Indiana, United States of America 46556.

Abstract

A complication of diabetes is the inability of wounds to heal in diabetic patients. Diabetic wounds are refractory to healing due to the involvement of activated matrix metalloproteinases (MMPs), which remodel the tissue resulting in apoptosis. There are no readily available methods that identify active unregulated MMPs. With the use of a novel inhibitor-tethered resin that binds exclusively to the active forms of MMPs, coupled with proteomics, we quantified MMP-8 and MMP-9 in a mouse model of diabetic wounds. Topical treatment with a selective MMP-9 inhibitor led to acceleration of wound healing, re-epithelialization, and significantly attenuated apoptosis. In contrast, selective pharmacological inhibition of MMP-8 delayed wound healing, decreased re-epithelialization, and exhibited high apoptosis. The MMP-9 activity makes the wounds refractory to healing, whereas that of MMP-8 is beneficial. The treatment of diabetic wounds with a selective MMP-9 inhibitor holds great promise in providing heretofore-unavailable opportunities for intervention of this disease.

PMID:
24053680
PMCID:
PMC3947039
DOI:
10.1021/cb4005468
[Indexed for MEDLINE]
Free PMC Article

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