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KMID : 0613820110210020183
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Journal of Life Science
2011 Volume.21 No. 2 p.183 ~ p.193
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Sphingosine-1-Phosphate-Induced Migration and Differentiation of Human Mesenchymal Stem Cells to Smooth Muscle Cells
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Song Hae-Young
Shin Sang-Hun
Kim Min-Young
Kim Jae-Ho
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Abstract
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Migration and differentiation of mesenchymal stem cells are crucial for tissue regeneration in response to injury. Sphingosine-1-phosphate (S1P) is a bioactive lipid that regulates a variety of biological processes, including proliferation, survival, differentiation and motility. In the present study, we determined the role of S1P in migration and differentiation of human bone marrow-derived mesenchymal stem cells (BMSCs). S1P stimulated migration of BMSCs in a dose- and time-dependent manner, and pre-incubation of the cells with pertussis toxin completely abrogated S1P-induced migration, suggesting involvement of Gi-coupled receptors in S1P-induced cell migration. S1P elicited elevation of intracellular concentration of () and pretreatment with VPC23019, an antagonist of , blocked S1P-induced migration and increase of . Small interfering RNA-mediated knockdown of endogenous attenuated S1P-induced migration of BMSCs. Furthermore, S1P treatment induced expression of -smooth muscle actin (-SMA), a smooth muscle marker, and pretreatment with VPC23019 abrogated S1P-induced -SMA expression. S1P induced phosphorylation of p38 mitogen-activated protein kinase (MAPK), and pretreatment of cells with SB202190, an inhibitor of p38 MAPK, or adenoviral overexpression of a dominant-negative mutant of the p38 MAPK blocked S1P-induced cell migration and -SMA expression. Taken together, these results suggest that S1P stimulates migration and smooth muscle differentiation of BMSCs through an -p38 MAPK-dependent mechanism.
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KEYWORD
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Sphingosine-1-phosphate, mesenchymal stem cells, migration, p38 MAPK, S1P receptor
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