Lysophosphatidic Acid (LPA) Activates ERK1/2-P90RSK Signaling in Porcine Trophoblast Cells

Abstract Text: LPA (lysophosphatidic acid) is a phospholipid having diverse biological effects on various types of tissues. Recently, we indicated that LPA and their specific G protein-coupled receptors appear to play a lipid regulator during implantation and establishment of pregnancy in a human, mice and pig.  In pig, LPA with various fatty acyl groups and receptors (LPA_1-3) were expressed in the uterine endometrium and conceptus during pregnancy. The extracellular-signal-regulated kinase (ERK1/2) pathway has emerged as one of the critical components in LPA signaling cascades.  However, little is known of the biological role of LPA in the porcine conceptus during implantation.  Therefore, this study examined LPA and the ERK1/2 signal transduction pathway in porcine conceptuses during early pregnancy.  The effects of LPA on the ERK1/2 signaling pathway were studied using established porcine trophectoderm cells (pTr) isolated from Day 12 pig conceptuses.  The pTr cells were serum starved for 24 h and then treated with LPA (0-20 uM) for 30 min. LPA dose dependently increased ERK1/2 phosphorylation. Western blot analyses of whole cell extracts with antibodies to target proteins also found that LPA increased levels of pERK1/2 and pP90RSK (ribosomal protein S6 kinase, 90kDa) by 2.3- and 1.6-fold, respectively, within 15 min which was maintained for up to 90 min.  MEK inhibitor U0126 and LPA₃ receptor blocker significantly decreased LPA-induced ERK and P90RSK activity. Collectively, these results indicate that LPA coordinately activates ERK1/2, P90RSK in pTr cells and supports the hypothesis that LPA is a critical regulator of trophoblast survival, growth and differentiation during early pregnancy.

Keywords: LPA, Pig trophoblast, ERK1/2