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- Title
Increased Matrix Metalloproteinase-9 in Wound Fluids Predicts Poor Wound Healing in Diabetic Foot Ulcers.
- Authors
Liu, Lisa; Natfaji, Anas; Lo, Lisa; Bolton, Thyra; Twigg, Stephen M.; Yue, Dennis; McLennan, Susan V.
- Abstract
Extracellular matrix turnover is a prerequisite for normal wound healing, however this needs to be regulated as uncontrolled proteolysis is a pathogenic factor in the non-healing of wounds. The matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs) and transforming growth factor-β (TGF-β) are important regulators of this wound remodelling process but there is very limited data on their impact on wound healing rate (WHR) in diabetes. The aim of this study was to investigate the relationship of MMP -2 & -9, TIMP-1 and TGF-β with WHR in diabetic patients with foot ulcers. Diabetic patients with foot ulcers (Texas Grading 0 - 2 and stage A or B ; initial ulcer area: 315±345mm²) attending our Foot Clinic were studied at presentation and subsequent follow up. Forty two patients (M/F 31/11, age 60.5±10.1yrs, diabetes duration 14.5±7.5yrs) were enrolled. The ulcers were debrided and exudates removed with saline. Wound fluid was collected by absorption onto a sterile 1 cm² filter paper and recovered by immersion in PBS. The MMP-2&-9 (active and pro forms) were analysed by quantitative zymography; TIMP-1 and TGF-β by ELISA. WHR was determined by NIH Image analysis of wound tracings and calculated as % change in ulcer area over 28 days. There was no relationship between wound area at presentation and levels of MMP-2,-9, TIMP-1 or TGF-β. The MMPs decreased whilst TIMP-1 and TGF-β increased progressively with wound healing. The MMP-9 level and MMP-9/TIMP-1 ratio, particulary the pro-form, correlated inversely with WHR at 28 days (r= -0.48 and r= - 0.57 respectively, p<0.001) but this relationship was not evident for MMP-2, TIMP-1 or TGF-β. The MMP-9 level and MMP-9/TIMP-1 ratio were also lower when results were analysed with respect to the 16 patients who achieved complete wound healing at wk 12 versus the 26 that did not (proMMP-9 : 5.2+4.2 vs 8.7+5.0 ng/ml; proMMP-9/TIMP-1 : 7.9+6.8 vs 34.0+49.6, p<0.05). These findings suggest that a milieu with low MMP-9 is conducive to wound healing. This could be related to the fact that MMP-9 is derived mainly from inflammatory cells and a high level may indicate the persistence of inflammation. Whether this observation is causally related to our previous finding of high wound bacterial count impeding healing remains to be determined. Measurement of MMP-9 and TIMP-1 in wound fluid may help to identify ulcers at risk of poor healing. Supported by Diabetes Australia Research Trust
- Subjects
METALLOPROTEINASES; WOUND healing; HEALING; DIABETIC foot; TRANSFORMING growth factors-beta
- Publication
Diabetes, 2007, Vol 56, pA66
- ISSN
0012-1797
- Publication type
Article