Lysophosphatidic acid receptors 2 and 3 regulate erythropoiesis at different hematopoietic stages
Journal
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Journal Volume
1866
Journal Issue
1
Date Issued
2021
Author(s)
Chiang, J.-C.
Chen, W.-M.
Lin, K.-H.
Hsia, K.
Ho, Y.-H.
Lin, Y.-C.
Lu, J.-H.
Yao, C.-L.
Chen, B.P.C.
Abstract
Hematopoiesis, the complex developmental process that forms blood components and replenishes the blood system, involves multiple intracellular and extracellular mechanisms. We previously demonstrated that lysophosphatidic acid (LPA), a lipid growth factor, has opposing regulatory effects on erythrocyte differentiation through activation of LPA receptors 2 and 3; yet the mechanisms underlying this process remain unclear. In this study, LPA2 is observed that highly expressed in common myeloid progenitors (CMP) in murine myeloid cells, whereas the expression of LPA3 displaces in megakaryocyte-erythroid progenitors (MEP) of later stage of myeloid differentiation. Therefore, we hypothesized that the switching expression of LPA2 and LPA3 determine the hematic homeostasis of mammalian megakaryocytic-erythroid lineage. In vitro colony-forming unit assays of murine progenitors reveal that LPA2 agonist GRI reduces the erythroblast differentiation potential of CMP. In contrast, LPA3 agonist OMPT increases the production of erythrocytes from megakaryocyte-erythrocyte progenitor cells (MEP). In addition, treatment with GRI reduces the erythroid, CMP, and MEP populations in mice, indicating that LPA2 predominantly inhibits myeloid differentiation at an early stage. In contrast, activation of LPA3 increases the production of terminally differentiated erythroid cells through activation of erythropoietic transcriptional factor. We also demonstrate that the LPA3 signaling is essential for restoration of phenylhydrazine (PHZ)-induced acute hemolytic anemia in mice and correlates to erythropoiesis impairment of Hutchinson-Gilford progeria Symptom (HGPS) premature aging expressed K562 model. Our results reveal the distinct roles of LPA2 and LPA3 at different stages of hematopoiesis in vivo, providing potentiated therapeutic strategies of anemia treatment. ? 2020 Elsevier B.V.
SDGs
Other Subjects
beta3 integrin; complementary DNA; erythroid kruppel like factor; erythromycin estolate; erythropoietin; Flt3 ligand; granulocyte macrophage colony stimulating factor; hemoglobin; interleukin 11; interleukin 6; lysophosphatidic acid receptor; lysophosphatidic acid receptor 2; lysophosphatidic acid receptor 3; messenger RNA; phenylhydrazine; thyroid peroxidase; transcription factor; transcription factor GATA 1; unclassified drug; 1-oleoyl-2-O-methyl-rac-glycerophosphothionate; isoquinoline derivative; Lpar3 protein, mouse; lysophosphatidic acid; lysophosphatidic acid receptor; lysophospholipid; phenylhydrazine; phenylhydrazine derivative; phosphatidic acid; phosphorothioic acid derivative; animal cell; animal experiment; animal model; Article; bone marrow cell; cell differentiation; cell lineage; cell proliferation; CFU counting; controlled study; erythroblast; erythrocyte; erythropoiesis; female; gene expression; hematopoiesis; hemoglobin blood level; hemolytic anemia; homeostasis; human; human cell; in vitro study; K-562 cell line; male; mammal; megakaryocyte; megakaryocyte erythroid progenitor; mouse; mRNA expression level; myeloid progenitor cell; nonhuman; premature aging; priority journal; progeria; signal transduction; animal; Bagg albino mouse; cytology; disease model; drug effect; erythroid cell; erythropoiesis; gene expression regulation; genetics; hemolytic anemia; metabolism; stem cell; Anemia, Hemolytic; Animals; Cell Differentiation; Cell Lineage; Disease Models, Animal; Erythroid Cells; Erythropoiesis; Gene Expression Regulation; Humans; Isoquinolines; K562 Cells; Lysophospholipids; Male; Mice; Mice, Inbred BALB C; Myeloid Cells; Organothiophosphates; Phenylhydrazines; Phosphatidic Acids; Receptors, Lysophosphatidic Acid; Stem Cells
Type
journal article