Pharmacological activation of lysophosphatidic acid receptors regulates erythropoiesis

Kuan Hung Lin, Ya Hsuan Ho, Jui Chung Chiang, Meng Wei Li, Shi Hung Lin, Wei Min Chen, Chi Ling Chiang, Yu Nung Lin, Ya Jan Yang, Chiung Nien Chen, Jenher Lu, Chang Jen Huang, Gabor Tigyi, Chao Ling Yao, Hsinyu Lee

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

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.

Original languageEnglish
Article number27050
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - May 31 2016
Externally publishedYes

ASJC Scopus subject areas

  • General

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