Decreased contraction of glycated collagen lattices coincides with impaired matrix metalloproteinase production

Nonenzymatic glycation of extracellular matrix (ECM) proteins is increased in diabetes mellitus and aging and triggers cellular events leading to an i mbalance in ECM homeostasis. We studied the influence of collagen glycation on matrix metalloproteinase production by dermal fibroblasts using the mod el of lattice cultures. Contraction of glycated collagen lattices was stron gly reduced when compared to controls. Meanwhile, fibroblasts synthesized l ower amounts of interstitial collagenase (MMP-1). Gelatinase A (MMP-2) prod uction was not modified, but its activation was strongly inhibited. These e ffects were independent from the intensity of lattice contraction and from any simultaneous modification of tissue inhibitors of metalloproteinase (TL MP-1 and 2) production. These results demonstrate that the impaired ability of fibroblasts to remodel and contract a glycated extracellular matrix coi ncides with a decrease in MMP production. (C) 1999 Academic Press.