Characterization of a TGFβ-responsive Human Trophoblast-derived Cell Line

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The placenta is formed by developing trophoblast cells to facilitate fluid, gas and nutrient exchange with the mother. Inappropriate trophoblast responsiveness can lead to life threatening complications during pregnancy including intrauterine growth retardation, pre-eclampsia, spontaneous abortion and malignancy that could lead to fetal loss. Transforming growth factor beta (TGFβ) is a multifunctional cytokine required for embryonic development and is an important regulator of human trophoblast function. Although TGFβ is critical for placental and embryonic development, there are currently no established TGFβ-responsive human trophoblast-derived cell lines available to study the mechanisms by which TGFβ regulates trophoblast function. Our studies have examined the transformed human trophoblast-derived cell line, ED27, to determine if it is responsive to TGFβ. Our data indicate that TGFβ dose responsively and reversibly inhibits cell growth in ED27cells and induces classic TGFβ response genes, fibronectin and plasminogen activator inhibitor 1 (PAI-1). TGFβ also induces an inhibitor of trophoblast invasion, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in ED27cells. Our studies have identified a human trophoblast-derived cell line that parallels isolated primary human trophoblasts in their responses to TGFβ. This cell line may provide us with the opportunity to determine TGFβ-mediated responses on human trophoblast functions not previously possible.



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