期刊
PHARMACOLOGICAL RESEARCH
卷 107, 期 -, 页码 243-248出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2016.03.008
关键词
Extracellular matrix; MMP-8; MMP-9; ND-336; Diabetic wounds
资金
- American Diabetes Association Pathway to Stop Diabetes [1-15-ACN-06]
Diabetic foot ulcers are a complication of diabetes for which treatment options are limited and not effective, resulting in 73,000 lower-limb amputations in the United States every year. Wound healing is a complex process with a highly orchestrated cascade of events, in which the extracellular matrix (ECM) interacts with growth factors and cells. Matrix metalloproteinases (MMPs) are involved in all wound healing events, in particular MMP-8 and MMP-9, whose physiological functions are to degrade damaged collagen type I and to facilitate keratinocyte migration and re-epithelialization, respectively. MMP substrate redundancy permits another MMP to substitute for MMP-9 during normal wound healing. Under the hypoxic and inflammatory environment of diabetic wounds, increased reactive oxygen species (ROS) and upregulation of MMP-9 results in wounds that are recalcitrant to healing. We have determined that MMP-8 plays a role in the body's response to wound healing and that MMP-9 is the pathological consequence of the disease with detrimental effects. Thus, selective inhibition of MMP-9, while leaving MMP-8 activity unaffected, is desirable. ND-336 has such inhibitory profile and is a promising strategy for treatment of diabetic foot ulcers. (C) 2016 Elsevier Ltd. All rights reserved.
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