Late remodeling of extracellular matrix after acute inflammatory injury or chronic distension

Abstract

Extracellular matrix remodeling is a crucial step in the healing process after inflammatory or infectious insult. We studied the role of matrix metalloproteinases in models of disease secondary to an acute inflammatory injury (burned skin) or chronic aggression (skin from obese patients submitted to gastroplasty). Skin samples were extracted using a 4 mm punch from abdomen of patients in late post-operative of bariatric surgery, recovered from third degree burns or control subjects. RNA was extracted by TRIzol and evaluated by quantitative PCR. MMPs activity was determined by zymography. In skin from burned patients, MMPs 2 and 9 expression was not different from control subjects. Obese patients present a higher MMP2 expression, compared to controls (2.4±0.56 x 1.0±0.1, respectively, p<0.05), however MMP9 mRNA was not detectable in these patients, even when conventional PCR was used. Interestingly, in spite of higher mRNA amounts, MMP2 activity was reduced in burned patients compared to controls (1.3±0.1 x 2.6±0.5 A.U., respectively, p<0.05), while MMP9 activity had a large variability, preventing any conclusion. We conclude that an acute inflammatory stimulus leads to late decreased MMP2 activity, what can explain the extensive fibrosis observed in these patients. In a more prolonged injury, due to chronic skin distension caused by obesity, MMP9 expression is affected leading to flabby skin deposits.