A chemical biological strategy to facilitate diabetic wound healing

Major Gooyit, Zhihong Peng, William R. Wolter, Hualiang Pi, Derong Ding, Dusan Hesek, Mijoon Lee, Bill Boggess, Matthew M. Champion, Mark A. Suckow, Shahriar Mobashery, Mayland Chang

Research output: Contribution to journalArticle

41 Scopus citations

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 reepithelialization, 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.

Original languageEnglish (US)
Pages (from-to)105-110
Number of pages6
JournalACS Chemical Biology
Volume9
Issue number1
DOIs
StatePublished - Jan 17 2014

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