神经酰胺激酶调节骨髓间充质干细胞的迁移。
Ceramide kinase regulates the migration of bone marrow-derived mesenchymal stem cells.
机构信息
Graduate School of Biotechnology, Kyung Hee University, Yongin, 17104, South Korea.
Department of Applied Chemistry, Kyung Hee University, Yongin, 17104, South Korea.
出版信息
Biochem Biophys Res Commun. 2019 Jan 8;508(2):361-367. doi: 10.1016/j.bbrc.2018.11.154. Epub 2018 Nov 28.
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.
内源性骨髓间充质干细胞（BM-MSCs）通过各种生长因子和细胞因子从外周血和损伤组织中动员，这些生长因子和细胞因子在损伤组织中表达，如 P 物质（SP）、基质细胞衍生因子-1（SDF-1）和转化生长因子-β（TGF-β）。细胞外生物活性脂质代谢物，如神经酰胺-1-磷酸和鞘氨醇-1-磷酸，也像 SP、SDF-1 和 TGF-β 一样调节 BM-MSC 的迁移。然而，BM-MSCs 中内在脂质激酶在干细胞迁移中的作用尚不清楚。在这里，我们证明神经酰胺激酶介导 BM-MSC 对 SP、SDF-1 或 TGF-β 的趋化迁移。此外，神经酰胺激酶的特异性抑制剂抑制 TGF-β诱导的 BM-MSC 迁移和 N-钙粘蛋白，N-钙粘蛋白是 BM-MSC 对 TGF-β 迁移所必需的。因此，这些结果表明细胞内神经酰胺激酶是 BM-MSCs 迁移所必需的，内在神经酰胺激酶在迁移中的作用与 N-钙粘蛋白的调节有关。
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