Matrix metalloproteinases and diabetic foot ulcers: the ratio of MMP-1 to TIMP-1 is a predictor of wound healing.
OBJECTIVE
Matrix metalloproteinases (MMPs) play a major role in wound healing: they can degrade all components of the extracellular matrix. In diabetic foot ulcers there is an excess of MMPs and a decrease of the tissue inhibitors of MMPs (TIMPs). This imbalance is probably one cause of impaired healing. However, little is known about changes in MMPs during wound healing.


METHODS
Sixteen patients with neuropathic diabetic foot ulcers participated. Wound fluid was collected regularly during the 12-week follow-up period, for measurement of MMP-1, MMP-2, MMP-8, MMP-9 and TIMP-1. Results were analysed by the degree of wound healing: good healers (defined by a reduction of at least 82% in initial wound surface at 4 weeks) and poor healers (reduction of less than 82% in wound surface at 4 weeks).


RESULTS
In good healers, levels of MMP-8 and -9 secreted by inflammatory cells decreased earlier. The initial levels of MMP-1 were similar in good and poor healers (P = 0.1) but rose significantly at week 2 in good healers (P = 0.039). There was a significant correlation between a high ratio of MMP-1/TIMP-1 and good healing (r = 0.65, P = 0.008). Receiver Operator Curve (ROC) analysis showed that an MMP-1/TIMP-1 ratio of 0.39 best predicted wound healing (sensitivity = 71%, specificity = 87.5%).


CONCLUSIONS
A high level of MMP-1 seems essential to wound healing, while an excess of MMP-8 and -9 is deleterious, and could be a target for new topical treatments. The MMP-1/TIMP-1 ratio is a predictor of wound healing in diabetic foot ulcers.
Muller
M
M
Department of Nephrology and Endocrinology, University Hospital, Grenoble, France.
Trocme
C
C
Lardy
B
B
Morel
F
F
Halimi
S
S
Benhamou
P Y
PY
D000368:Aged; D000369:Aged, 80 and over; D001826:Body Fluids / Q000201:enzymology; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology*; D017719:Diabetic Foot / Q000201:enzymology* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005109:Extracellular Matrix / Q000201:enzymology; D005260:Female; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D016896:Treatment Outcome; D014945:Wound Healing / Q000502:physiology*
D019715:Tissue Inhibitor of Metalloproteinase-1; D020781:Matrix Metalloproteinase 1