Matrix metalloproteinases (MMPs) are a class of zinc-dependent endopeptidases involved in extracellular matrix degradation and remodeling. Activation of the MMPs can be initiated in vitro by treatment with detergents, organomercurials, and oxidants. Activation can also be initiated proteolytically using trypsin or plasmin. It has been shown for collagenase to obtain maximal collagenolytic activity in vitro that it must be co-activated with stromelysin-1, which results in a 7-12-fold increase in activity. The purpose of this investigation was to determine whether the addition of exogenous stromelysin-1 affects the ability of live cells to degrade collagen. A cell-mediated collagen degradation system was utilized to analyze the ability of stromelysin-1 to superactivate collagenase in cell cu'ture. Human fibroblast seeded in a single colony on reconstituted rat tail tendon type I collagen in the presence of trypsin or plasminogen were capable of degrading the collagen beneath them in 2-3 days. However, collagenolytic activity was greatly enhanced by the addition of stromelysin-1 in combination with trypsin or plasminogen above that seen with just stromelysin-1, trypsin, or plasminogen. This was clearly seen by the increased area of collagen cleavage. This will indicate that these cells produce latent collagenase that is dependent on an external activating factor and stromelysin-1 for maximal collagenolyic activity. This work was supported by USPHS grants P50 DE08228, RO1 DE10631, and P50 CA13148.
|Original language||English (US)|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology