Increased matrix metalloproteinase-9 predicts poor wound healing in diabetic foot ulcers.
OBJECTIVE
We studied the relationships of diabetic ulcer wound fluid matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and transforming growth factor-beta1 (TGF-beta1) with wound healing rate.


METHODS
The ulcers were cleansed to remove exudates, and wound fluids were collected for analysis of MMP-2 and -9, TIMP-1, and TGF-beta1.


RESULTS
At presentation, MMP-9 and the MMP-9-to-TIMP-1 ratio correlated inversely with the wound healing rate at 28 days (P < 0.001). MMP-9 and the MMP-9-to-TIMP-1 ratio were lower in the 23 patients who achieved complete healing at 12 weeks versus the 39 who did not. The pro-MMP-9 concentration was predictive of healing within 12 weeks. Addition of cutoffs for TIMP-1 (>480 pg/ml) and TGF-beta (>115 pg/ml) further improved its predictive power (area under the curve 0.94).


CONCLUSIONS
These findings suggest that a milieu with high MMP-9 may be indicative of inflammation and poor wound healing. Measurements of MMP-9, TIMP-1, and TGF-beta in wound fluid may help to identify ulcers at risk of poor healing.
Discipline of Medicine, University of Sydney, Sydney, Australia.
Yu
Y
Liu
Danqing
D
Min
Thyra
T
Bolton
Vanessa
V
Nubé
Stephen M
SM
Twigg
Dennis K
DK
Yue
Susan V
SV
McLennan
D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D017719:Diabetic Foot / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology*; D005260:Female; D016523:Foot Ulcer / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
D000900:Anti-Bacterial Agents; D006442:Glycated Hemoglobin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1