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Targeting MMP-9 in Diabetic Foot Ulcers

Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA
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Author to whom correspondence should be addressed.
Pharmaceuticals 2019, 12(2), 79; https://doi.org/10.3390/ph12020079
Received: 1 May 2019 / Revised: 15 May 2019 / Accepted: 18 May 2019 / Published: 22 May 2019
(This article belongs to the Special Issue Matrix Metalloproteinases)
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Abstract

Diabetic foot ulcers (DFUs) are significant complications of diabetes and an unmet medical need. Matrix metalloproteinases (MMPs) play important roles in the pathology of wounds and in the wound healing process. However, because of the challenge in distinguishing active MMPs from the two catalytically inactive forms of MMPs and the clinical failure of broad-spectrum MMP inhibitors in cancer, MMPs have not been a target for treatment of DFUs until recently. This review covers the discovery of active MMP-9 as the biochemical culprit in the recalcitrance of diabetic wounds to healing and targeting this proteinase as a novel approach for the treatment of DFUs. Active MMP-8 and MMP-9 were observed in mouse and human diabetic wounds using a batimastat affinity resin and proteomics. MMP-9 was shown to play a detrimental role in diabetic wound healing, whereas MMP-8 was beneficial. A new class of selective MMP-9 inhibitors shows clinical promise for the treatment of DFUs. View Full-Text
Keywords: matrix metalloproteinase-9; diabetic foot ulcers; wound healing; MMP-9 inhibitors matrix metalloproteinase-9; diabetic foot ulcers; wound healing; MMP-9 inhibitors
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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MDPI and ACS Style

Jones, J.I.; Nguyen, T.T.; Peng, Z.; Chang, M. Targeting MMP-9 in Diabetic Foot Ulcers. Pharmaceuticals 2019, 12, 79.

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