title: Pharmacological activation of lysophosphatidic acid receptors regulates erythropoiesis.
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 (LPA3) 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 LPA2 enhanced erythropoiesis, whereas knockdown of LPA3 inhibited RBC differentiation. In CD34(+) human hematopoietic stem cells (hHSC) and K526 cells, the LPA3 agonist 1-oleoyl-2-methyl-sn-glycero-3-phosphothionate (2S-OMPT) promoted erythropoiesis, whereas the LPA2 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 LPA2 and LPA3 play opposing roles during RBC differentiation. The pharmacological activation of LPA receptor subtypes represent a novel strategies for augmenting or inhibiting erythropoiesis.
authors.affiliation: Department of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Kuan-Hung
authors.initials: KH
authors.lastname: Lin
authors.affiliation: Department of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Ya-Hsuan
authors.initials: YH
authors.lastname: Ho
authors.affiliation: Department of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Jui-Chung
authors.initials: JC
authors.lastname: Chiang
authors.affiliation: Department of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Meng-Wei
authors.initials: MW
authors.lastname: Li
authors.affiliation: Department of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Shi-Hung
authors.initials: SH
authors.lastname: Lin
authors.affiliation: Department of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Chen
authors.affiliation: School of Biomedical Science, Ohio State University, Columbus, OH, USA.
authors.forename: Chi-Ling
authors.initials: CL
authors.lastname: Chiang
authors.affiliation: Department of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Yu-Nung
authors.initials: YN
authors.lastname: Lin
authors.affiliation: Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan.
authors.forename: Ya-Jan
authors.initials: YJ
authors.lastname: Yang
authors.affiliation: Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: Chiung-Nien
authors.initials: CN
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Jenher
authors.initials: J
authors.lastname: Lu
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
authors.forename: Chang-Jen
authors.initials: CJ
authors.lastname: Huang
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Gabor
authors.initials: G
authors.lastname: Tigyi
authors.affiliation: Department of Chemical Engineering and Materials Science, Yuan Ze University, Taoyuan, Taiwan.
authors.forename: Chao-Ling
authors.initials: CL
authors.lastname: Yao
authors.affiliation: Department of Life Science, National Taiwan University, Taipei, Taiwan.|Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan.|Angiogenesis Research Center, National Taiwan University, Taipei, Taiwan.|Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan.|Center for Biotechnology, National Taiwan University, Taipei, Taiwan.
authors.forename: Hsinyu
authors.initials: H
authors.lastname: Lee
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D004625:Embryo, Nonmammalian; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004920:Erythropoiesis / Q000187:drug effects* / Q000235:genetics; D004921:Erythropoietin / Q000494:pharmacology; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006454:Hemoglobins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D020014:K562 Cells; D008246:Lysophospholipids / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010755:Organophosphates / Q000494:pharmacology; D063086:Organothiophosphates / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000494:pharmacology; D020033:Protein Isoforms / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish
chemical_list: C473891:1-oleoyl-2-O-methyl-rac-glycerophosphothionate; C554270:EPO protein, human; D006454:Hemoglobins; D008246:Lysophospholipids; D010755:Organophosphates; D063086:Organothiophosphates; D010712:Phosphatidic Acids; D020033:Protein Isoforms; D049368:Receptors, Lysophosphatidic Acid; D004921:Erythropoietin; C032881:lysophosphatidic acid