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Consistent with this view, our in vitro experiments demonstrated that increasing MMP-9 expression promotes collagen breakdown and apoptosis in rat amnions in organ culture. It should be noted that cells remaining anchored to the amnion, in addition to those that had separated from their substrates, were undergoing apoptosis as evidenced by nuclear DNA fragmentation. Hence, apoptosis appears to be initiated before complete separation of the amnion cells from their substrate, perhaps as a result of partial detachment or changes in cell shape due to matrix degradation.
The MMP inhibitor batimastat prevented the amnion cell apoptosis induced by AdMMP-9. This inhibitor is not specific for MMP-9, so we cannot conclude that it’s effects were solely on MMP-9. It is possible that other MMPs are activated by AdMMP-9 infection and that these enzymes participate in the induction of apoptosis. ventolin 100 mcg
We corroborated the rat amnion organ culture studies by using cultures of human amnion cells (WISH cells) grown in serum-free medium on a combined matrix of type I and type IV collagen. Transfection of the WISH cells with an MMP-9 expression plasmid resulted in cell detachment and apoptosis, whereas transfection of the cells with an empty vector had no effect on cell attachment and cell death (unpublished observations).
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