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Elevated matrix metalloproteinase-2 and -3 production from human diabetic dermal fibroblasts
S J Wall1, M J Sampson, N Levell
1School of Biological Sciences, University of East Anglia, Norwich, NR4 7TJ, U.K.
Background:
Diabetic foot ulcers are characterized by elevated levels of matrix metalloproteinases (MMP), which could lead to excessive matrix breakdown and disruption to healing. It is unknown if this elevation is a function of wound healing, or if it is present within normal skin and a primary contributor to the increased risk of impaired healing.
Objectives:
To determine whether diabetic fibroblasts from unwounded skin show elevated MMP production compared with their nondiabetic counterparts.
Patients And Methods:
Circular skin biopsies (4 mm diameter) were taken from the inside upper arm of four controls without diabetes and from four subjects with insulin-treated diabetes. Fibroblasts were incubated for a further 72 h and conditioned medium was collected and stored at -20 degrees C. The conditioned medium was assessed by gelatin zymography and Western blotting for MMP-2 and MMP-3.
Results:
Diabetic dermal fibroblasts showed significantly elevated production of MMP-2 (P < 0.05) and pro-MMP-3 (P < 0.05) when compared with their nondiabetic counterparts.
Conclusions:
Dermal fibroblasts from normal unwounded skin are characterized by increased MMP production and this may be a primary contributing factor to the increased risk of nonhealing foot ulceration in diabetes.
