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A chemical biological strategy to facilitate diabetic wound healing.

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.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Gooyit M,Peng Z,Wolter WR,Pi H,Ding D,Hesek D,Lee M,Boggess B,Champion MM,Suckow MA,Mobashery S,Chang M

doi

10.1021/cb4005468

subject

Has Abstract

pub_date

2014-01-17 00:00:00

pages

105-10

issue

1

eissn

1554-8929

issn

1554-8937

journal_volume

9

pub_type

杂志文章

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