Sphingosylphosphorylcholine induces proliferation of human adipose tissue-derived mesenchymal stem cells via activation of JNK
Sphingosylphosphorylcholine (SPC) has been implicated in a variety of cellular responses, including proliferation and differentiation. In this study, we demonstrate that d-erythro-SPC, but not l-threo-SPC, stereoselectively stimulated the proliferation of human adipose tissue-derived mesenchymal ste...
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| Format: | Article |
| Language: | English |
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Elsevier
2006-03-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520336191 |
| _version_ | 1818646746625998848 |
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| author | Eun Su Jeon Hae Young Song Mi Ra Kim Hyun Jung Moon Yong Chan Bae Jin Sup Jung Jae Ho Kim |
| author_facet | Eun Su Jeon Hae Young Song Mi Ra Kim Hyun Jung Moon Yong Chan Bae Jin Sup Jung Jae Ho Kim |
| author_sort | Eun Su Jeon |
| collection | DOAJ |
| description | Sphingosylphosphorylcholine (SPC) has been implicated in a variety of cellular responses, including proliferation and differentiation. In this study, we demonstrate that d-erythro-SPC, but not l-threo-SPC, stereoselectively stimulated the proliferation of human adipose tissue-derived mesenchymal stem cells (hADSCs), with a maximal increase at 5 μM, and increased the intracellular concentration of Ca2+ ([Ca2+]i) in hADSCs, which do not express known SPC receptors (i.e., OGR1, GPR4, G2A, and GPR12). The SPC-induced proliferation and increase in [Ca2+]i were sensitive to pertussis toxin (PTX) and the phospholipase C (PLC) inhibitor U73122, suggesting that PTX-sensitive G proteins, Gi or Go, and PLC are involved in SPC-induced proliferation. In addition, SPC treatment induced the phosphorylation of c-Jun and extracellular signal-regulated kinase, and SPC-induced proliferation was completely prevented by pretreatment with the c-Jun N-terminal kinase (JNK)-specific inhibitor SP600125 but not with the MEK-specific inhibitor U0126. Furthermore, the SPC-induced proliferation and JNK activation were completely attenuated by overexpression of a dominant negative mutant of JNK2, and the SPC-induced activation of JNK was inhibited by pretreatment with PTX or U73122. Treatment of hADSCs with lysophosphatidic acid (LPA) receptor antagonist, Ki16425, had no impact on the SPC-induced increase in [Ca2+]i. However, SPC-induced proliferation was partially, but significantly, attenuated by pretreatment of the cells with Ki16425.These results indicate that SPC stimulates the proliferation of hADSCs through the Gi/Go-PLC-JNK pathway and that LPA receptors may be responsible in part for the SPC-induced proliferation. |
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| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T00:51:32Z |
| publishDate | 2006-03-01 |
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| series | Journal of Lipid Research |
| spelling | doaj.art-a9821b4cd8a54e2683c7fedb594e25702022-12-21T22:09:45ZengElsevierJournal of Lipid Research0022-22752006-03-01473653664Sphingosylphosphorylcholine induces proliferation of human adipose tissue-derived mesenchymal stem cells via activation of JNKEun Su Jeon0Hae Young Song1Mi Ra Kim2Hyun Jung Moon3Yong Chan Bae4Jin Sup Jung5Jae Ho Kim6Research Center for Ischemic Tissue Regeneration, Pusan National University, Busan 602-739, Republic of Korea; Department of Plastic Surgery, College of Medicine, Pusan National University, Busan 602-739, Republic of Korea; Medical Research Institute, Pusan National University, Busan 602-739, Republic of KoreaResearch Center for Ischemic Tissue Regeneration, Pusan National University, Busan 602-739, Republic of Korea; Department of Plastic Surgery, College of Medicine, Pusan National University, Busan 602-739, Republic of Korea; Medical Research Institute, Pusan National University, Busan 602-739, Republic of KoreaResearch Center for Ischemic Tissue Regeneration, Pusan National University, Busan 602-739, Republic of Korea; Department of Plastic Surgery, College of Medicine, Pusan National University, Busan 602-739, Republic of Korea; Medical Research Institute, Pusan National University, Busan 602-739, Republic of KoreaResearch Center for Ischemic Tissue Regeneration, Pusan National University, Busan 602-739, Republic of Korea; Department of Plastic Surgery, College of Medicine, Pusan National University, Busan 602-739, Republic of Korea; Medical Research Institute, Pusan National University, Busan 602-739, Republic of KoreaResearch Center for Ischemic Tissue Regeneration, Pusan National University, Busan 602-739, Republic of Korea; Department of Plastic Surgery, College of Medicine, Pusan National University, Busan 602-739, Republic of Korea; Medical Research Institute, Pusan National University, Busan 602-739, Republic of KoreaResearch Center for Ischemic Tissue Regeneration, Pusan National University, Busan 602-739, Republic of Korea; Department of Plastic Surgery, College of Medicine, Pusan National University, Busan 602-739, Republic of Korea; Medical Research Institute, Pusan National University, Busan 602-739, Republic of KoreaResearch Center for Ischemic Tissue Regeneration, Pusan National University, Busan 602-739, Republic of Korea; Department of Plastic Surgery, College of Medicine, Pusan National University, Busan 602-739, Republic of Korea; Medical Research Institute, Pusan National University, Busan 602-739, Republic of KoreaSphingosylphosphorylcholine (SPC) has been implicated in a variety of cellular responses, including proliferation and differentiation. In this study, we demonstrate that d-erythro-SPC, but not l-threo-SPC, stereoselectively stimulated the proliferation of human adipose tissue-derived mesenchymal stem cells (hADSCs), with a maximal increase at 5 μM, and increased the intracellular concentration of Ca2+ ([Ca2+]i) in hADSCs, which do not express known SPC receptors (i.e., OGR1, GPR4, G2A, and GPR12). The SPC-induced proliferation and increase in [Ca2+]i were sensitive to pertussis toxin (PTX) and the phospholipase C (PLC) inhibitor U73122, suggesting that PTX-sensitive G proteins, Gi or Go, and PLC are involved in SPC-induced proliferation. In addition, SPC treatment induced the phosphorylation of c-Jun and extracellular signal-regulated kinase, and SPC-induced proliferation was completely prevented by pretreatment with the c-Jun N-terminal kinase (JNK)-specific inhibitor SP600125 but not with the MEK-specific inhibitor U0126. Furthermore, the SPC-induced proliferation and JNK activation were completely attenuated by overexpression of a dominant negative mutant of JNK2, and the SPC-induced activation of JNK was inhibited by pretreatment with PTX or U73122. Treatment of hADSCs with lysophosphatidic acid (LPA) receptor antagonist, Ki16425, had no impact on the SPC-induced increase in [Ca2+]i. However, SPC-induced proliferation was partially, but significantly, attenuated by pretreatment of the cells with Ki16425.These results indicate that SPC stimulates the proliferation of hADSCs through the Gi/Go-PLC-JNK pathway and that LPA receptors may be responsible in part for the SPC-induced proliferation.http://www.sciencedirect.com/science/article/pii/S0022227520336191c-Jun N-terminal kinasephospholipase CG proteins |
| spellingShingle | Eun Su Jeon Hae Young Song Mi Ra Kim Hyun Jung Moon Yong Chan Bae Jin Sup Jung Jae Ho Kim Sphingosylphosphorylcholine induces proliferation of human adipose tissue-derived mesenchymal stem cells via activation of JNK Journal of Lipid Research c-Jun N-terminal kinase phospholipase C G proteins |
| title | Sphingosylphosphorylcholine induces proliferation of human adipose tissue-derived mesenchymal stem cells via activation of JNK |
| title_full | Sphingosylphosphorylcholine induces proliferation of human adipose tissue-derived mesenchymal stem cells via activation of JNK |
| title_fullStr | Sphingosylphosphorylcholine induces proliferation of human adipose tissue-derived mesenchymal stem cells via activation of JNK |
| title_full_unstemmed | Sphingosylphosphorylcholine induces proliferation of human adipose tissue-derived mesenchymal stem cells via activation of JNK |
| title_short | Sphingosylphosphorylcholine induces proliferation of human adipose tissue-derived mesenchymal stem cells via activation of JNK |
| title_sort | sphingosylphosphorylcholine induces proliferation of human adipose tissue derived mesenchymal stem cells via activation of jnk |
| topic | c-Jun N-terminal kinase phospholipase C G proteins |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520336191 |
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