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 imbalance in ECM homeostasis. We studied the influence of collagen glycation on matrix metalloproteinase production by dermal fibroblasts using the model of lattice cultures. Contraction of glycated collagen lattices was strongly reduced when compared to controls. Meanwhile, fibroblasts synthesized lower amounts of interstitial collagenase (MMP-1). Gelatinase A (MMP-2) production was not modified, but its activation was strongly inhibited. These effects were independent from the intensity of lattice contraction and from any simultaneous modification of tissue inhibitors of metalloproteinase (TIMP-1 and 2) production. These results demonstrate that the impaired ability of fibroblasts to remodel and contract a glycated extracellular matrix coincides with a decrease in MMP production.
Rittié
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Laboratory of Biochemistry and Molecular Biology, CNRS UPRESA 6021, IFR 53-Biomolécules, Faculty of Medicine, University of Reims Champagne-Ardenne, 51 Rue Cognacq-Jay, 51095 Reims cedex, France.
Berton
A
A
Monboisse
J C
JC
Hornebeck
W
W
Gillery
P
P
D000328:Adult; D002478:Cells, Cultured; D003094:Collagen / Q000031:analogs & derivatives*; D017077:Culture Media, Conditioned; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D011487:Protein Conformation; D012867:Skin; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis
D017077:Culture Media, Conditioned; D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1