Targeting MMP-9 in Diabetic Foot Ulcers

Pharmaceuticals - Tập 12 Số 2 - Trang 79
Jeffrey I. Jones1, Trung T. Nguyen1, Zhihong Peng1, Mayland Chang1
1Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA

Tóm tắt

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.

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Tài liệu tham khảo

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