Involvement of ERK1/2 pathway in TGF‐β1‐induced VEGF secretion in normal human cytotrophoblast cells

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Abstract
Transforming growth factor‐β1 (TGF‐β1) plays a pivotal role in the angiogenesis during the development of placenta, but the intracellular signaling mechanism by which TGF‐β1 stimulates this process remains poorly understood. In this article, we demonstrated that exposure of normal human cytotrophoblast cells to TGF‐β1 stimulated the secretion of the VEGF gene encoding vascular endothelial growth factor, which is a key factor in angiogenesis. Meanwhile, treatment of normal human cytotrophoblast cells with TGF‐β1‐induced expression of HIF‐1a, the regulated subunit of hypoxia‐inducible factor 1, a known transactivator of the VEGF gene. Our data indicated that TGF‐β1 induced extracellular signal‐ regulated kinase (ERK) 1/2 phosphorylation in normal human cytotrophoblast cells. Moreover, treating cells with PD98059, an inhibitor of ERK1/2 signaling, inhibited TGF‐β1 stimulation of VEGF secretion and HIF‐1a protein expression. These data indicated that in normal human cytotrophoblast cells, TGF‐β1 induced HIF‐1a‐mediated VEGF secretion, and TGF‐β1‐stimulated‐ERK1/2 activation may be involved in this process. Mol. Reprod. Dev. 68: 198–204, 2004.

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