title: Opposing regulation of megakaryopoiesis by LPA receptors 2 and 3 in K562 human erythroleukemia cells.
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.
authors.affiliation: Department of Life Science, National Taiwan University, Taipei, Taiwan, ROC.
authors.forename: Ya-Hsuan
authors.initials: YH
authors.lastname: Ho
authors.affiliation: Department of Chemical Engineering and Materials Science, Yuan-Ze University, Chung-Li, Taiwan, ROC.
authors.forename: Chao-Ling
authors.initials: CL
authors.lastname: Yao
authors.affiliation: Department of Life Science, National Taiwan University, Taipei, Taiwan, ROC.
authors.forename: Kuan-Hung
authors.initials: KH
authors.lastname: Lin
authors.affiliation: Department of Life Science, National Taiwan University, Taipei, Taiwan, ROC.
authors.forename: Fen-Han
authors.initials: FH
authors.lastname: Hou
authors.affiliation: Department of Life Science, National Taiwan University, Taipei, Taiwan, ROC.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Chen
authors.affiliation: School of Biomedical Science, The Ohio State University, Columbus, USA.
authors.forename: Chi-Ling
authors.initials: CL
authors.lastname: Chiang
authors.affiliation: Department of Life Science, National Taiwan University, Taipei, Taiwan, ROC.
authors.forename: Yu-Nung
authors.initials: YN
authors.lastname: Lin
authors.affiliation: Department of Life Science, National Taiwan University, Taipei, Taiwan, ROC.
authors.forename: Meng-Wei
authors.initials: MW
authors.lastname: Li
authors.affiliation: Department of Life Science, National Taiwan University, Taipei, Taiwan, ROC.
authors.forename: Shi-Hung
authors.initials: SH
authors.lastname: Lin
authors.affiliation: Department of Life Science, National Taiwan University, Taipei, Taiwan, ROC.
authors.forename: Ya-Jan
authors.initials: YJ
authors.lastname: Yang
authors.affiliation: Department of Life Science, National Taiwan University, Taipei, Taiwan, ROC.
authors.forename: Chu-Cheng
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Department of Pediatrics and Pediatric Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. Electronic address: jenherlu@gmail.com.
authors.forename: Jenher
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center Memphis, Memphis, USA. Electronic address: gtigyi@physio1.uthsc.edu.
authors.forename: Gabor
authors.initials: G
authors.lastname: Tigyi
authors.affiliation: Department of Life Science, National Taiwan University, Taipei, Taiwan, ROC; Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan, ROC; Angiogenesis Research Center, National Taiwan University, Taipei, Taiwan, ROC; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan, ROC; Center for Biotechnology, National Taiwan University, Taipei, Taiwan, ROC. Electronic address: hsinyu@ntu.edu.tw.
authors.forename: Hsinyu
authors.initials: H
authors.lastname: Lee
mesh_terms: D050982:GATA1 Transcription Factor / Q000378:metabolism; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics / Q000378:metabolism*; D008533:Megakaryocytes / Q000187:drug effects / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D034061:Thrombopoiesis / Q000187:drug effects; D013997:Time Factors; D015534:Trans-Activators; D014162:Transfection; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; C098179:FLII protein, human; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; C061248:ITGB3 protein, human; D039661:Integrin beta3; D008840:Microfilament Proteins; D017382:Reactive Oxygen Species; D018160:Receptors, Cytoplasmic and Nuclear; D049368:Receptors, Lysophosphatidic Acid; D015534:Trans-Activators; D051176:beta Catenin; D013755:Tetradecanoylphorbol Acetate
keywords: CD61; Hematopoiesis; LPA receptor; Lysophosphatidic acid; Megakaryopoiesis; Phorbol ester