Pharmacological activation of lysophosphatidic acid receptors regulates erythropoiesis

Kuan Hung Lin; Ya Hsuan Ho; Jui Chung Chiang; Meng Wei Li; Shi Hung Lin; Wei Min Chen; Chi Ling Chiang; Yu Nung Lin; Ya Jan Yang; Chiung Nien Chen; Jenher Lu; Chang Jen Huang; Gabor Tigyi; Chao Ling Yao; Hsinyu Lee

doi:10.1038/srep27050

Pharmacological activation of lysophosphatidic acid receptors regulates erythropoiesis

Kuan Hung Lin, Ya Hsuan Ho, Jui Chung Chiang, Meng Wei Li, Shi Hung Lin, Wei Min Chen, Chi Ling Chiang, Yu Nung Lin, Ya Jan Yang, Chiung Nien Chen, Jenher Lu, Chang Jen Huang, Gabor Tigyi, Chao Ling Yao, Hsinyu Lee

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Abstract

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.

Original language	English
Article number	27050
Journal	Scientific Reports
Volume	6
DOIs	https://doi.org/10.1038/srep27050
Publication status	Published - May 31 2016
Externally published	Yes

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@article{76453bf02ab642fcaa24ed53327aa4e0,

title = "Pharmacological activation of lysophosphatidic acid receptors regulates erythropoiesis",

abstract = "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.",

author = "Lin, {Kuan Hung} and Ho, {Ya Hsuan} and Chiang, {Jui Chung} and Li, {Meng Wei} and Lin, {Shi Hung} and Chen, {Wei Min} and Chiang, {Chi Ling} and Lin, {Yu Nung} and Yang, {Ya Jan} and Chen, {Chiung Nien} and Jenher Lu and Huang, {Chang Jen} and Gabor Tigyi and Yao, {Chao Ling} and Hsinyu Lee",

note = "Funding Information: Acknowledgements This research was supported by grants (NSC 100-2325-B-002-045, NHRI 101-EX102-10130BI, NTU 102R76263A) to H. Lee and grants (MOST 101-2221-E-155 -044 -MY3) to CL. Yao from the National Science Council/Ministry of Science and Technology, National Health Research Institutes, and National Taiwan University of the Republic of China and grants from NIAID AI080405 (GT), the NCI CA092160 (GT). Copyright: Copyright 2016 Elsevier B.V., All rights reserved.",

year = "2016",

month = may,

day = "31",

doi = "10.1038/srep27050",

language = "English",

volume = "6",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

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T1 - Pharmacological activation of lysophosphatidic acid receptors regulates erythropoiesis

AU - Lin, Kuan Hung

AU - Ho, Ya Hsuan

AU - Chiang, Jui Chung

AU - Li, Meng Wei

AU - Lin, Shi Hung

AU - Chen, Wei Min

AU - Chiang, Chi Ling

AU - Lin, Yu Nung

AU - Yang, Ya Jan

AU - Chen, Chiung Nien

AU - Lu, Jenher

AU - Huang, Chang Jen

AU - Tigyi, Gabor

AU - Yao, Chao Ling

AU - Lee, Hsinyu

N1 - Funding Information: Acknowledgements This research was supported by grants (NSC 100-2325-B-002-045, NHRI 101-EX102-10130BI, NTU 102R76263A) to H. Lee and grants (MOST 101-2221-E-155 -044 -MY3) to CL. Yao from the National Science Council/Ministry of Science and Technology, National Health Research Institutes, and National Taiwan University of the Republic of China and grants from NIAID AI080405 (GT), the NCI CA092160 (GT). Copyright: Copyright 2016 Elsevier B.V., All rights reserved.

PY - 2016/5/31

Y1 - 2016/5/31

N2 - 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.

AB - 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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Pharmacological activation of lysophosphatidic acid receptors regulates erythropoiesis

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