Roles of FGF-4 on the Differentiation of Trophoblast Stem (TS) Cells / 대한해부학회지

ABSTRACT

Fibroblast growth factor-4 (FGF-4) has various functions, affecting many signaling pathways, and leading to cellular proliferation and differentiation and to the regulation of cell migration, invasion, and angiogenesis. However, there are few reports of the relationship between TS cells and FGF-4 even if FGF-4 is located in inner cell mass of embryo and Fibroblast growth factor receptor (FGFR) is located in TS cells. Therefore the physiologic effects of FGF-4 on TS cells were investigated for identifying the effects of FGF-4 on TS ell differentiation. FGF-4 was involved in early stage development of the trophoblast via upregulation of eomesodermin mRNA expression. In addition, FGF-4 suppressed the differentiation of TS cells through activation of extracellular-signal regulated kinase (Erk) and suppression of focal adhesion kinase (FAK) activation, which in TS cells is an important indicator of early trophoblast cell differentiation, migration and invasion. FGF-4 was involved in angiogenesis in the trophoblast through the activation of p38 and the induction of Dlx-3 mRNA expression in TS cells. In addition, TS cells cultured with FGF-4 for 4 days in a thrombinfibrinogen gel culture system, a specific culture system for endothelial cells, showed a healthy appearance, while TS cells cultured without FGF-4 were severely damaged. Taken together, these data suggest that FGF-4 is closely involved in differentiation of TS cells for development of placenta.