TY - JOUR
T1 - A chemical biological strategy to facilitate diabetic wound healing
AU - Gooyit, Major
AU - Peng, Zhihong
AU - Wolter, William R.
AU - Pi, Hualiang
AU - Ding, Derong
AU - Hesek, Dusan
AU - Lee, Mijoon
AU - Boggess, Bill
AU - Champion, Matthew M.
AU - Suckow, Mark A.
AU - Mobashery, Shahriar
AU - Chang, Mayland
PY - 2014/1/17
Y1 - 2014/1/17
N2 - 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.
AB - 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.
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U2 - 10.1021/cb4005468
DO - 10.1021/cb4005468
M3 - Article
C2 - 24053680
AN - SCOPUS:84898867762
SN - 1554-8929
VL - 9
SP - 105
EP - 110
JO - ACS Chemical Biology
JF - ACS Chemical Biology
IS - 1
ER -
