Opposing regulation of megakaryopoiesis by LPA receptors 2 and 3 in K562 human erythroleukemia cells

Ya Hsuan Ho, Chao Ling Yao, Kuan Hung Lin, Fen Han Hou, Wei Min Chen, Chi Ling Chiang, Yu Nung Lin, Meng Wei Li, Shi Hung Lin, Ya Jan Yang, Chu Cheng Lin, Jenher Lu, Gabor Tigyi, Hsinyu Lee

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Erythrocytes and megakaryocytes (MK) are derived from a common progenitor that undergoes lineage specification. Lysophosphatidic acid (LPA), a lipid growth factor was previously shown to be a regulator for erythropoietic process through activating LPA receptor 3 (LPA3). However, whether LPA affects megakaryopoiesis remains unclear. In this study, we used K562 leukemia cell line as a model to investigate the roles of LPA in MK differentiation. We demonstrated that K562 cells express both LPA2 and LPA3, and the expression levels of LPA2 are higher than LPA3. Treatment with phorbol 12-myristate 13-acetate, a commonly used inducer of megakaryopoiesis, reciprocally regulates the expressions of LPA2 and LPA3. By pharmacological blockers and knockdown experiments, we showed that activation of LPA2 suppresses whereas, LPA3 promotes megakaryocytic differentiation in K562. The LPA2-mediated inhibition is dependent on β-catenin translocation, whereas reactive oxygen species (ROS) generation is a downstream signal for activation of LPA3. Furthermore, the hematopoietic transcriptional factors GATA-1 and FLI-1, appear to be involved in these regulatory mechanisms. Taken together, our results suggested that LPA2 and LPA3 may function as a molecular switch and play opposing roles during megakaryopoiesis of K562 cells.

Original languageEnglish
Pages (from-to)172-183
Number of pages12
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1851
Issue number2
DOIs
Publication statusPublished - Feb 2015
Externally publishedYes

Keywords

  • CD61
  • Hematopoiesis
  • LPA receptor
  • Lysophosphatidic acid
  • Megakaryopoiesis
  • Phorbol ester

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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