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Ceramide kinase regulates the migration of bone marrow-derived mesenchymal stem cells

Yu, Jinyeong, Kim, Hye Min, Kim, Kwang Pyo, Son, Youngsook, Kim, Min-Sik, Park, Ki-Sook
Biochemical and biophysical research communications 2019 v.508 no.2 pp. 361-367
blood, bone marrow, cadherins, cell movement, ceramides, chemotaxis, cytokines, mesenchymal stromal cells, metabolites, phosphates, phosphotransferases (kinases), sphingosine, stem cells, substance P, transforming growth factor beta
Endogenous bone marrow-derived mesenchymal stem cells (BM-MSCs) are mobilized into peripheral blood and injured tissues by various growth factors and cytokines that are expressed in the injured tissues, such as substance P (SP), stromal cell derived factor-1 (SDF-1), and transforming growth factor-beta (TGF-β). Extracellular bioactive lipid metabolites such as ceramide-1-phosphate and sphingosine-1-phosphate also modulate BM-MSC migration as SP, SDF-1, and TGF-β. However, the roles of intrinsic lipid kinases of BM-MSCs in the stem cell migration are unclear. Here, we demonstrated that ceramide kinase mediates the chemotactic migration of BM-MSCs in response to SP, SDF-1, or TGF-β. Furthermore, a specific inhibitor of ceramide kinase inhibited TGF-β-induced migration of BM-MSCs and N-cadherin that is necessary for BM-MSCs migration in response to TGF-β. Therefore, these results suggest that the intracellular ceramide kinase is required for the BM-MSCs migration and the roles of the intrinsic ceramide kinase in the migration are associated with N-cadherin regulation.