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Pharmacological activation of lysophosphatidic acid receptors regulates erythropoiesis.
- Source :
-
Scientific reports [Sci Rep] 2016 May 31; Vol. 6, pp. 27050. Date of Electronic Publication: 2016 May 31. - Publication Year :
- 2016
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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.
- Subjects :
- Animals
Embryo, Nonmammalian
Erythrocytes cytology
Erythrocytes drug effects
Erythrocytes metabolism
Erythropoiesis genetics
Erythropoietin pharmacology
Gene Expression Regulation
Hematopoietic Stem Cells cytology
Hematopoietic Stem Cells metabolism
Hemoglobins antagonists & inhibitors
Hemoglobins biosynthesis
Hemoglobins genetics
Humans
K562 Cells
Lysophospholipids pharmacology
Mice
Mice, Inbred BALB C
Organophosphates pharmacology
Organothiophosphates pharmacology
Phosphatidic Acids pharmacology
Protein Isoforms agonists
Protein Isoforms genetics
Protein Isoforms metabolism
Receptors, Lysophosphatidic Acid agonists
Receptors, Lysophosphatidic Acid metabolism
Zebrafish
Cell Differentiation drug effects
Erythropoiesis drug effects
Hematopoietic Stem Cells drug effects
Lysophospholipids metabolism
Receptors, Lysophosphatidic Acid genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 27244685
- Full Text :
- https://doi.org/10.1038/srep27050