期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 834, 期 -, 页码 77-83出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2018.07.014
关键词
Matrix metalloproteinase-9; Aclerastide; Diabetic foot ulcers; Reactive oxygen species; Angiotensin II
资金
- American Diabetes Association Pathway to Stop Diabetes [1-15-ACN-06]
- National Institutes of Health [T32 GM075762]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM075762] Funding Source: NIH RePORTER
Chronic wounds are a complication of diabetes. Treatment for diabetic foot ulcers is complex with little clinical recourse, resulting in 108,000 lower-limb amputations annually in the United States alone. Matrix metalloproteinases (MMPs) play important roles in the pathology and in the repair of chronic wounds. We previously identified active MMP-8 and MMP-9 in wounds of diabetic mice and determined that MMP-8 accelerates wound repair, while MMP-9 is the culprit for the diabetic wound being refractory to healing. Aclerastide, a peptide analog of angiotensin II, recently failed in phase III clinical trials for treatment of diabetic foot ulcers. We demonstrate herein that treatment of wounds of diabetic mice with aclerastide results in elevated levels of reactive oxygen species and of active MMP-9, which is likely an important contributor to the failure of aclerastide in clinical trials.
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