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LPA receptor 2 and 3 reversely regulate TPA‐induced megakaryopoiesis in K562 leukemia cell line (1094.3)
Author(s) -
Ho YaHsuan,
Lin KuanHung,
Lin YuNung,
Li MengWei,
Lin ShihHung,
Yang YaJan,
Chiang ChiLing,
Yao ChaoLing,
Lee Hsinyu
Publication year - 2014
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.28.1_supplement.1094.3
Subject(s) - lysophosphatidic acid , gene knockdown , autotaxin , microbiology and biotechnology , receptor , signal transduction , cell culture , chemistry , biology , cancer research , medicine , biochemistry , genetics
Erythrocytes and megakaryocytes (MK) are derived from a common progenitor that undergoes lineage specification. Recently, lysophosphatidic acid (LPA), a lipid growth factor that regulates diverse cellular responses through activating LPA receptors, is shown to be a regulator in erythropoiesis. However, whether LPA is involved during megakaryopoiesis process remains unclear. In this study, we use K562 leukemia cell line as a model to investigate the roles of LPA in megakaryopoiesis. Our data demonstrate that expression levels of LPA receptor 2 (LPA2) is relatively higher than LPA3 in K562 cells. Phorbol 12‐myristate 13‐acetate (TPA), a commonly used megakaryopoiesis inducer in K562, increases LPA2 expression levels 24 hours after treatment, and decreases significantly after 48 hours. In contrast, TPA treatment increases LPA3 expression levels continuously. By monitoring mRNA and protein expression levels of MK marker CD61, blockade of LPA1/3 signaling by 20 μM Ki16425 inhibits TPA‐induced megakaryopoiesis. Moreover, activation of LPA3 signaling by 500 nM OMPT treatment enhances megakaryopoiesis. On the contrary, activation of LPA2 signaling by 10 μM MDP treatment suppresses megakaryopoiesis. Furthermore, knockdown of LPA3 by siRNA impairs megakaryopoiesis, while knockdown of LPA2 enhances megakaryopoiesis. These results suggest that, by monitoring CD61 expression, LPA2 and LPA3 inversely regulate megakaryopoiesis in K562 cells.