Cell-mediated degradation of type IV collagen and gelatin films is dependent on the activation of matrix metalloproteinases.
The ability of normal rabbit dermal fibroblasts to degrade films of type IV collagen and gelatin when stimulated by phorbol ester was shown to be dependent on the induction, secretion and activation of 95 kDa gelatinase B and the secretion and activation of 72 kDa gelatinase A and stromelysin. Degradation was inhibited by exogenous human recombinant tissue inhibitor of metalloproteinases-1, specific antibodies to gelatinase and stromelysin and by the reactive-oxygen-metabolite inhibitor catalase. We discuss the various pathways for activation of matrix metalloproteinases in this model system and conclude that, although plasmin may play a key role in the activation of gelatinase B and stromelysin, gelatinase A is activated by a mechanism which has yet to be elucidated. The involvement of oxygen radicals in the direct activation of matrix metalloproteinases in this model is thought to be unlikely.
Atkinson
S J
SJ
Cell and Molecular Biology Department, Strangeways Research Laboratory, Cambridge, U.K.
Ward
R V
RV
Reynolds
J J
JJ
Murphy
G
G
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism*; D004789:Enzyme Activation; D005780:Gelatin / Q000378:metabolism; D006023:Glycoproteins / Q000494:pharmacology; D066298:In Vitro Techniques; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000378:metabolism*; D010618:Phenanthrolines / Q000494:pharmacology; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D010618:Phenanthrolines; D017382:Reactive Oxygen Species; D019714:Tissue Inhibitor of Metalloproteinases; D005780:Gelatin; D003094:Collagen; D002374:Catalase; D017364:Collagenases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D013755:Tetradecanoylphorbol Acetate; C025205:1,10-phenanthroline