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Pharmacological activation of LPA receptors regulates erythro‐megakaryocytic differentiation in myeloid lineage
Author(s) -
Chiang JuiChung,
Lin KuanHung,
Ho YaShuan,
Yao ChaoLing,
Lee Hsinyu
Publication year - 2016
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.30.1_supplement.748.3
Subject(s) - erythropoiesis , haematopoiesis , myeloid , megakaryocyte , receptor , microbiology and biotechnology , biology , cellular differentiation , agonist , progenitor cell , chemistry , stem cell , cancer research , medicine , biochemistry , gene , anemia
Myeloid cell differentiation is one of the crucial process of hematopoiesis. It has been revealed that lysophosphatidic acid (LPA), through activating G‐protein‐coupled receptors of LPA 1–6 , may contribute to the regulation of this process. However, the underlie mechanisms in vivo remains unclear. Here, we aim to investigate the effects of LPA and its corresponding receptors, LPA 2 and LPA 3 , during erythropoiesis/megakaryopoiesis. Two chemical drugs, LPA 2 agonist GRI977143 and LPA 3 agonist 1‐oleoyl‐2‐O‐methyl‐rac‐glycerophosphothionate (OMPT) were injected in BALB/ c mice. Blood samples were collected and analyzed to determine the quantity of differentiation‐stage‐specific erythro‐megakaryocytic progenitors in spleen/bone marrow and terminally differentiated cells in circulatory blood, respectively. Our results revealed that the activation of LPA 2 inhibit erythro‐megakaryocytic differentiation, whereas activation of LPA 3 may promote erythroid development and decrease megakaryocyte generation in vivo . These result implied that LPA 2 may dominate and inhibit the erythro‐megakaryocytic differentiation in the early stage of myeloid lineage. In contrast, LPA 3 mainly regulates and promotes erythroid differentiation except for megakaryocyte. Taken together, our findings showing a remarkable difference between LPA receptor activation on regulating hematopoiesis in vivo. Moreover, the detailed impacts of LPA 2/3 on different stages of myeloid stem cells during erythropoiesis/megakaryopoiesis will be elucidated in the future.

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