Open AccessPharmacological activation of lysophosphatidic acid receptors regulates erythropoiesis
Author(s) -
Kuan Hung Lin,
Ya Hsuan Ho,
JuiChung Chiang,
Meng Wei Li,
Shi Hung Lin,
Wei Min Chen,
ChiLing Chiang,
YihBin Lin,
Ya-Chien Yang,
Chiung Nien Chen,
JenHer Lu,
Chang Jen Huang,
Gábor Tigyi,
ChaoLing Yao,
Hsinyu Lee
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep27050
Subject(s) - lysophosphatidic acid , erythropoiesis , erythropoietin , receptor , agonist , gene knockdown , biology , microbiology and biotechnology , haematopoiesis , endocrinology , medicine , chemistry , stem cell , biochemistry , anemia , apoptosis
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.