PUBLICATION

Pharmacological activation of lysophosphatidic acid receptors regulates erythropoiesis

Authors

Lin, K.H., Ho, Y.H., Chiang, J.C., Li, M.W., Lin, S.H., Chen, W.M., Chiang, C.L., Lin, Y.N., Yang, Y.J., Chen, C.N., Lu, J., Huang, C.J., Tigyi, G., Yao, C.L., Lee, H.

ID

ZDB-PUB-160601-1

Date

2016

Source

Scientific Reports 6: 27050 (Journal)

Registered Authors

Huang, Chang-Jen

Keywords

Haematopoietic stem cells, Lipid signalling

MeSH Terms

Receptors, Lysophosphatidic Acid/agonists
Receptors, Lysophosphatidic Acid/genetics*
Receptors, Lysophosphatidic Acid/metabolism
Erythropoiesis/drug effects*
Erythropoiesis/genetics
Erythrocytes/cytology
Erythrocytes/drug effects
Erythrocytes/metabolism
Gene Expression Regulation
Hemoglobins/antagonists & inhibitors
Hemoglobins/biosynthesis
Hemoglobins/genetics
Erythropoietin/pharmacology
Organophosphates/pharmacology
K562 Cells
Cell Differentiation/drug effects*
Phosphatidic Acids/pharmacology
Animals
Embryo, Nonmammalian
Lysophospholipids/metabolism*
Lysophospholipids/pharmacology
Protein Isoforms/agonists
Protein Isoforms/genetics
Protein Isoforms/metabolism
Mice, Inbred BALB C
Hematopoietic Stem Cells/cytology
Hematopoietic Stem Cells/drug effects*
Hematopoietic Stem Cells/metabolism
Zebrafish
Humans
Mice
Organothiophosphates/pharmacology

(all 32)

PubMed

27244685 Full text @ Sci. Rep.

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.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
hbaa1	WT	standard conditions	Long-pec	nucleate erythrocyte	ISH	Fig. 4
hbaa1	WT	standard conditions	Day 4	nucleate erythrocyte	ISH	Fig. 5
hbaa1	WT	chemical treatment: (2S)-1-oleoyl-2-methylglycero-3-phosphothionate	Day 4	nucleate erythrocyte	ISH	Fig. 5
hbaa1	WT + MO2-lpar3	standard conditions	Day 4	nucleate erythrocyte	ISH	Fig. 5
hbaa1	WT + MO2-lpar3	standard conditions	Long-pec	nucleate erythrocyte	ISH	Fig. 4
hbbe1.1	WT	standard conditions	Long-pec	myeloid cell	ISH	Fig. 4
hbbe1.1	WT	chemical treatment: (2S)-1-oleoyl-2-methylglycero-3-phosphothionate	Day 4	nucleate erythrocyte	ISH	Fig. 5
hbbe1.1	WT	standard conditions	Day 4	nucleate erythrocyte	ISH	Fig. 5
hbbe1.1	WT + MO2-lpar3	standard conditions	Long-pec	myeloid cell	ISH	Fig. 4
hbbe1.1	WT + MO2-lpar3	standard conditions	Day 4	nucleate erythrocyte	ISH	Fig. 5

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT	chemical treatment: (2S)-1-oleoyl-2-methylglycero-3-phosphothionate	Day 4	hemoglobin biosynthetic process increased occurrence, abnormal	Fig. 5
WT	chemical treatment: (2S)-1-oleoyl-2-methylglycero-3-phosphothionate	Day 4	nucleate erythrocyte hbaa1 expression increased amount, abnormal	Fig. 5
WT	chemical treatment: (2S)-1-oleoyl-2-methylglycero-3-phosphothionate	Day 4	nucleate erythrocyte hbbe1.1 expression increased amount, abnormal	Fig. 5
WT	chemical treatment: GRI977143	Day 4	hemoglobin biosynthetic process decreased occurrence, abnormal	Fig. 6
WT	chemical treatment: KI16425	Long-pec	hemoglobin biosynthetic process decreased occurrence, abnormal	Fig. 4
WT + MO1-lpar2a	standard conditions	Day 4	hemoglobin biosynthetic process increased occurrence, abnormal	Fig. 6
WT + MO2-lpar3	standard conditions	Day 4	hemoglobin biosynthetic process decreased occurrence, abnormal	Fig. 5
WT + MO2-lpar3	chemical treatment: (2S)-1-oleoyl-2-methylglycero-3-phosphothionate	Day 4	hemoglobin biosynthetic process occurrence, ameliorated	Fig. 5

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Mutations / Transgenics

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
lpar2a	MO1-lpar2a	MRPHLNO
lpar3	MO2-lpar3	MRPHLNO

Fish

Fish
WT
WT + MO1-lpar2a
WT + MO2-lpar3

Antibodies

Orthology

Engineered Foreign Genes

Mapping

Lin et al., 2016 ZDB-PUB-160601-1 PMID:27244685

Pharmacological activation of lysophosphatidic acid receptors regulates erythropoiesis

Lin et al., 2016

ZDB-PUB-160601-1
PMID:27244685