Pharmacological activation of lysophosphatidic acid receptors regulates erythropoiesis
Journal
Scientific Reports
Journal Volume
6
Pages
27050
Date Issued
2016
Author(s)
Lin K.-H.
Ho Y.-H.
Chiang J.-C.
Li M.-W.
Lin S.-H.
Chen W.-M.
Chiang C.-L.
Lin Y.-N.
Yang Y.-J.
Lu J.
Huang C.-J.
Tigyi G.
Yao C.-L.
Abstract
Abstract Lysophosphatidic acid (LPA), a growth factor-like phospholipid, regulates numerous physiological functions, including cell proliferation and differentiation. In a previous study, we have demonstrated that LPA activates erythropoiesis by activating the LPA 3 receptor subtype (LPA 3 ) under erythropoietin (EPO) induction. In the present study, we applied a pharmacological approach to further elucidate the functions of LPA receptors during red blood cell (RBC) differentiation. In K562 human erythroleukemia cells, knockdown of LPA 2 enhanced erythropoiesis, whereas knockdown of LPA 3 inhibited RBC differentiation. In CD34 + human hematopoietic stem cells (hHSC) and K526 cells, the LPA 3 agonist 1-oleoyl-2-methyl-sn-glycero-3-phosphothionate (2S-OMPT) promoted erythropoiesis, whereas the LPA 2 agonist dodecyl monophosphate (DMP) and the nonlipid specific agonist GRI977143 (GRI) suppressed this process. In zebrafish embryos, hemoglobin expression was significantly increased by 2S-OMPT treatment but was inhibited by GRI. Furthermore, GRI treatment decreased, whereas 2S-OMPT treatment increased RBC counts and amount of hemoglobin level in adult BALB/c mice. These results indicate that LPA 2 and LPA 3 play opposing roles during RBC differentiation. The pharmacological activation of LPA receptor subtypes represent a novel strategies for augmenting or inhibiting erythropoiesis.
SDGs
Publisher
Nature Publishing Group
Type
journal article