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Lysophosphatidic Acid Regulates Erythropoiesis at Different Hematopoietic Hierarchy
Author(s) -
Chiang JuiChung,
Lin KuanHung,
Chen WeiMin,
Lee Hsinyu
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.705.4
Subject(s) - haematopoiesis , myelopoiesis , erythropoiesis , lysophosphatidic acid , microbiology and biotechnology , biology , myeloid , progenitor cell , agonist , thrombopoiesis , chemistry , megakaryocyte , receptor , medicine , immunology , stem cell , biochemistry , anemia
Hematopoiesis, a complex developmental process to form blood components and replenish 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 activating LPA receptor 2 and 3, yet the underlie mechanisms in vivo remained unclear. Examining the LPA receptors expression profile in murine myeloid cells indicates that LPA 2 is highly expressed on common myeloid progenitor (CMP), whereas expression of LPA 3 increases with later erythrocyte differentiation. Therefore, we hypothesize that the expression of LPA 2 and LPA 3 determine the hematic homeostasis of mammalian hematopoietic progenitors. In vitro colony forming unit (CFU) assays of murine sorted progenitor cells reveal that LPA 2 agonist, GRI977143, reduces the erythroblast differentiation potential of CMP. In contrast, LPA 3 agonist,1‐oleoyl‐2‐O‐methyl‐rac‐glycerophosphothionate (OMPT), increases the production of erythrocyte from megakaryocyte erythrocyte progenitor (MEP). In addition, LPA 2 agonist treatment reduces erythroid, CMP and MEP populations in mice. These results indicate that activation of LPA 2 predominantly inhibits myeloid differentiation at the early stage of myelopoiesis. By contrast, activation of LPA 3 increases production of terminally differentiated erythroid cells. We also demonstrate that LPA 3 agonist successfully restored phenylhydrazine (PHZ)‐induced acute hemolytic anemia in mice. Our results reveal distinct roles of LPA 2 and LPA 3 at different hematopoietic hierarchy in vivo , suggesting potential therapeutic strategies for the treatment of anemia. Support or Funding Information This research was supported by a grant from Ministry of Science and Technology, Taiwan (MOST 107‐2311‐B‐002‐009‐) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .