Lysophosphatidic acid activates β-catenin/T cell factor signaling, which contributes to the suppression of apoptosis in H19-7 cells.

Lysophosphatidic acid (LPA) is a lipid growth factor that regulates diverse cell functions, including cell proliferation, survival and apoptosis. LPA has been demonstrated to be involved in the regulation of cortical neurogenesis by increasing the survival of neural precursors. Previously, we reported that LPA stimulated the inactivation of glycogen synthase kinase 3 (GSK3) via the G protein-coupled LPA1 and LPA2 receptors, by which apoptosis is suppressed in H19-7 cells [an embryonic hippocampal progenitor cell (HPC) line]. Increasing numbers of studies have demonstrated that certain G protein-coupled receptors activate β-catenin/T cell factor (TCF) signaling independently of Wnt, which is involved in cell fate determination, cell proliferation and cell survival. To determine whether LPA activates β-catenin-mediated transcriptional activation pathways and whether β-catenin/TCF signaling is involved in neurogenesis by controlling the survival of neural precursors, β-catenin/TCF signaling cascades induced by LPA were investigated in the HPCs. Activation of β-catenin/TCF signaling was determined by the nuclear translocation of β-catenin and the transcriptional activation of a TCF reporter gene. The activation of β-catenin/TCF signaling was blocked by pertussis toxin (PTX) and a protein kinase C (PKC) inhibitor. The expression of a constitutively active mutated form of GSK3β activated β-catenin/TCF signaling to comparable levels to those induced by LPA, and protected against apoptosis in differentiating H19-7 cells. These results showed that LPA activates β-catenin/TCF signaling in a PTX- and PKC-dependent manner, which contributes to LPA-induced cell survival in the HPCs. Activation of β-catenin/TCF signaling by LPA may be involved in neurogenesis by controlling the survival of neural precursors.

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