LPA Induces Erythropoiesis Process Through Activating LPA Receptor 3

Abstract

Lysophosphatidic acid (LPA), an extracellular lipid mediator, exerts multiple bioactivities through an activating family set of G-protein-coupled receptors (GPCRs). LPA receptor 3 (EDG7) is a member of endothelial differentiation gene (EDG) family receptors, which regulates in differentiation and development in circulation system. In zebrafish study using the zlpa3 anti-sense morpholino oligonucletids (zlpa3-Mo), hemopoietic defects was observed in the injected embryos. Cultured cord blood-derived human hemopoietic stem cells (hHSCs) could be induced to differentiate into mature erythrocytes in vitro by erythropoietin (EPO) and stem cell factor (SCF) stimulation. Erythroblasts express mRNA transcripts for both LPA1 and LPA3. Ki16425, a completive antagonist of LPA1 and LPA3, blocked the erythropoietic differentiation as detected through mRNA and protein expression of CD71 (Transferrin receptor protein 1) and GlyA (Glycophorin A). Furthermore, specifically knockdown LPA3, but not LPA1, blocked the erythropoiesis process. In addition, LPA enhanced the differentiation of erythroblasts in the plasma-free culture in a concentration dependant manner. By immunefluorescence analysis, translocation of β-catenin into nucleus, a downstream response of LPA receptor activation, was blocked by Ki16425 treatment. In conclusion, LPA participates in EPO dependant erythropoiesis process through activating LPA3, and β-catenin may be involved in this process.