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Epidermal Growth Factor and Basic Fibroblast Growth Factor Increase the Production of Matrix Metalloproteinases during in Vitro Decidualization of Rat Endometrial Stromal Cells
Numerous growth factors are involved in mediating proliferation and
differentiation of endometrial stromal cells during decidualization.
During this period, the extracellular matrix of the endometrium
undergoes extensive remodeling. We tested the hypothesis that epidermal
growth factor (EGF), basic fibroblast growth factor (bFGF), and
transforming growth factor-β regulate expression of matrix
metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of
metalloproteinases (TIMPs), during decidualization. Stromal cells were
isolated from uteri hormonally sensitized to undergo decidualization
and were cultured in the absence or presence of a growth factor. Using
substrate-gel electrophoresis with gelatin as the substrate, we
detected activity for gelatinase A and B, and collagenase-3, and using
casein as a substrate, we detected activity for stromelysin-1.
Increasing concentrations of EGF and bFGF resulted in increased
activity of gelatinase B, collagenase-3, and stromelysin-1. Northern
blot analyses revealed that EGF and bFGF also increased messenger RNA
levels for these MMPs. There was no effect of these growth factors on
gelatinase or TIMP-1, -2, and -3, nor was there an effect of
transforming growth factor-β on any MMP or TIMP examined. These data
demonstrate that EGF and bFGF increase levels of proteolytic enzymes
produced by endometrial stromal cells undergoing decidualization
in vitro while having no effect on their inhibitors.