title: Sphingosine-1-phosphate/S1P receptors signaling modulates cell migration in human bone marrow-derived mesenchymal stem cells.
abstract: The recruitment of bone marrow-derived mesenchymal stem cells (BMSCs) to damaged tissues and sites of inflammation is an essential step for clinical therapy. However, the signals regulating the motility of these cells are still not fully understood. Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, is known to have a variety of biological effects on various cells. Here, we investigated the roles of S1P and S1P receptors (S1PRs) in migration of human BMSCs. We found that S1P exerted a powerful migratory action on human BMSCs. Moreover, by employing RNA interference technology and pharmacological tools, we demonstrated that S1PR1 and S1PR3 are responsible for S1P-induced migration of human BMSCs. In contrast, S1PR2 mediates the inhibition of migration. Additionally, we explored the downstream signaling pathway of the S1P/S1PRs axis and found that activation of S1PR1 or S1PR3 increased migration of human BMSCs through a G i /extracellular regulated protein kinases 1/2- (ERK1/2-) dependent pathway, whereas activation of S1PR2 decreased migration through the Rho/Rho-associated protein kinase (ROCK) pathway. In conclusion, we reveal that the S1P/S1PRs signaling axis regulates the migration of human BMSCs via a dual-directional mechanism. Thus, selective modulation of S1PR's activity on human BMSCs may provide an effective approach to immunotherapy or tissue regeneration.
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China ; Beijing Key Laboratory of Emerging Infectious Diseases, Jingshundongjie 8, Beijing 100015, China.
authors.forename: Yaxian
authors.initials: Y
authors.lastname: Kong
authors.affiliation: Stem Cell Research Center, Peking University, Beijing 100191, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China ; Beijing Key Laboratory of Emerging Infectious Diseases, Jingshundongjie 8, Beijing 100015, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Lin
authors.affiliation: Stem Cell Research Center, Peking University, Beijing 100191, China.
authors.forename: Shuling
authors.initials: S
authors.lastname: Wang
mesh_terms: D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D008246:Lysophospholipids / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D000081025:Sphingosine-1-Phosphate Receptors
chemical_list: D008246:Lysophospholipids; D049349:Receptors, Lysosphingolipid; C477362:S1PR1 protein, human; D000081025:Sphingosine-1-Phosphate Receptors; C577483:sphingosine-1-phosphate receptor-3, human; C060506:sphingosine 1-phosphate; D013110:Sphingosine