Regulation of cell motile activity through the different induction of LPA receptors by estrogens in liver epithelial WB-F344 cells

► LPA signaling is involved in cell migration by estrogens in WB-F344 cells. ► 17β-Estradiol and ethinyl estradiol enhanced cell migration activity through LPA3. ► Diethylstilbestrol suppressed cell migration activity through LPA1. ► LPA1 inhibited and LPA3 increased cell migration activity of WB-F344 cells. Lysophosphatidic acid (LPA) interacts with G protein-coupled transmembrane LPA receptors (LPA receptors; LPA1–LPA6). Recently, we demonstrated that each LPA receptor acts as a positive or negative regulator of cell migration ability. It is known that estrogens indicate a variety of biological functions, including cell motility. In the present study, to assess whether LPA signaling is involved in cell motile activity stimulated by estrogens, we measured cell motile activity and LPA receptor expressions of rat liver epithelial WB-F344 cells treated with 17β-estradiol (E2), ethinyl estradiol (EE) and diethylstilbestrol (DES) at concentrations of 0.1 and 1.0μM for 48h. The cell motility of E2 and EE treated cells was significantly higher than that of untreated cells. By contrast, DES markedly inhibited cell motile activity. Using quantitative real time RT–PCR analysis, Lpar1 and Lpar3 expressions in E2 treated cells were significantly higher than those in untreated cells. In EE treated cells, Lpar3 expression was markedly elevated, whereas Lpar1 expression was decreased. On the other hand, Lpar1 expression was significantly increased in DES treated cells. Interestingly, the effects of E2, EE and DES on cell motility were suppressed by Lpar1 or Lpar3 knockdown. These results suggest that the different induction of LPA receptors by estrogens may regulate cell motile activity of WB-F344 cells.