Expression of matrix-metalloproteinases and their inhibitors in the wounds of diabetic and non-diabetic patients

Aims/hypothesis. The molecular factors that cause an acute wound in diabetic patients to become chronic have not yet been established. Wound healing is known to require a balance between the accumulation of collagenous and non-collagenous extracellular matrix components and their remodelling by matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs). Our aim was to assess if the concentrations of MMPs and TIMPs were different between acute and chronic wounds in diabetic patients by analysing biopsy samples. Methods. A 5 turn punch biopsy was taken from 20 diabetic foot ulcers of patients before initiating treatment and from traumatic wounds of 12 non-diabetic patients 2 days after injury. The concentrations of MMP-1, MMP-2(pro), MMP-2(active), MMP-8, MMP-9 and TIMP-2 were measured in detergent extracts of the biopsy homogenates using ELISAs and gelatine-zymography. Results. The concentration of MMP-1 was increased 65-fold in biopsies of diabetic foot ulcers compared with the concentrations measured in biopsies of traumatic wounds. Similarly, MMP-2(pro) were increased threefold, sixfold for MMP-2(active), twofold for MMP-8 and 14-fold for MMP-9 compared to average concentrations in biopsies of traumatic wounds. Furthermore, the expression of TIMP-2 was reduced twofold in diabetic wounds compared with lesions of non-diabetic patients. Conclusion/interpretation. The combination of increased concentrations of MMPs with decreased concentrations of TIMP-2 in chronic diabetic foot ulcers compared with healing wounds in normal patients suggests that the increased proteolytic environment contributes to the failure of diabetic wounds to heal. New treatment strategies for healing chronic diabetic foot ulcers could be directed towards reducing concentrations of MMPs and increasing levels of TIMPs.