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Ceramide kinase regulates the migration of bone marrow-derived mesenchymal stem cells
Authors:Jinyeong Yu  Hye Min Kim  Kwang Pyo Kim  Youngsook Son  Min-Sik Kim  Ki-Sook Park
Affiliation:1. Graduate School of Biotechnology, Kyung Hee University, Yongin, 17104, South Korea;2. Department of Applied Chemistry, Kyung Hee University, Yongin, 17104, South Korea;3. Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul, 02447, South Korea;4. Department of New Biology, DGIST, Daegu, 42988, South Korea;5. East-West Medical Research Institute, Kyung Hee University, Seoul, 02447, South Korea;6. Kyung Hee University Medical Center, Seoul, 02447, South Korea
Abstract: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.
Keywords:Ceramide kinase  Mesenchymal stem cells  Migration  TGF-β  N-cadherin
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