Pharmacological activation of lysophosphatidic acid receptors regulates erythropoiesis | Zendy

KuanHung Lin | Zendy; Ya-Hsuan Ho | Zendy; JuiChung Chiang | Zendy; Meng-Wei Li | Zendy; Shi-Hung Lin | Zendy; WeiMin Chen | Zendy; ChiLing Chiang | Zendy; Yunung Nina Lin | Zendy; Ya-Jan Yang | Zendy; ChiungNien Chen | Zendy; JenHer Lu | Zendy; Chang-Jen Huang | Zendy; Gábor Tigyi | Zendy; ChaoLing Yao | Zendy; Hsinyu Lee | Zendy

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Pharmacological activation of lysophosphatidic acid receptors regulates erythropoiesis

Author(s) -

KuanHung Lin,

Ya-Hsuan Ho,

JuiChung Chiang,

Meng-Wei Li,

Shi-Hung Lin,

WeiMin Chen,

ChiLing Chiang,

Yunung Nina Lin,

Ya-Jan Yang,

ChiungNien Chen,

JenHer Lu,

Chang-Jen Huang,

Gábor Tigyi,

ChaoLing Yao,

Hsinyu Lee

Publication year - 2016

Publication title -

scientific reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.24

H-Index - 213

ISSN - 2045-2322

DOI - 10.1038/srep27050

Subject(s) - lysophosphatidic acid , erythropoiesis , erythropoietin , receptor , agonist , gene knockdown , biology , microbiology and biotechnology , haematopoiesis , endocrinology , medicine , chemistry , stem cell , biochemistry , anemia , apoptosis

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 (LPA 3 ) 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 LPA 2 enhanced erythropoiesis, whereas knockdown of LPA 3 inhibited RBC differentiation. In CD34 + human hematopoietic stem cells (hHSC) and K526 cells, the LPA 3 agonist 1-oleoyl-2-methyl-sn-glycero-3-phosphothionate (2S-OMPT) promoted erythropoiesis, whereas the LPA 2 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 LPA 2 and LPA 3 play opposing roles during RBC differentiation. The pharmacological activation of LPA receptor subtypes represent a novel strategies for augmenting or inhibiting erythropoiesis.

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