title: Restructuring of the extracellular matrix in diabetic wounds and healing: A perspective.
abstract: 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.
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, United States. Electronic address: mchang@nd.edu.
authors.forename: Mayland
authors.initials: M
authors.lastname: Chang
mesh_terms: D000818:Animals; D048909:Diabetes Complications / Q000188:drug therapy*; D005109:Extracellular Matrix / Q000187:drug effects; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D020780:Matrix Metalloproteinase 9
keywords: Diabetic wounds; Extracellular matrix; MMP-8; MMP-9; ND-336