Glycosphingolipids regulate ameloblastin expression in dental epithelial cells
Glycosphingolipids regulate ameloblastin expression in dental epithelial cells
复制标题
鞘糖脂调节牙上皮细胞中的成釉细胞蛋白表达
DOI：
10.1177/0022034511424408
复制
发表时间：
2012
影响因子：
7.6
通讯作者：
et al
中科院分区：
文献类型：
--
作者：
Kamasaki;et al
神经营养素4（NT-4）及其受体调节成釉细胞在牙齿发育中的分化。神经节苷脂是一种含有鞘糖脂的唾液酸，参与多种膜相关细胞生理功能，如配体-受体信号传递。然而，GSL在牙齿发育过程中的表达模式和功能尚不清楚。在这项研究中，我们确定了GM 3和LacCer在牙上皮细胞中的强表达，这引起了成釉细胞的分化。外源性GM 3和LacCer诱导牙上皮细胞表达成釉蛋白（Ambn），同时GM 3协同增强NT-4介导的Ambn表达。此外，外源性GM 3和LacCer可诱导细胞外信号调节激酶1/2（ERK 1/2）的激活，这是Ambn表达的上游事件，而D-PcR去除牙上皮细胞GSL可抑制Ambn的表达和ERK 1/2的磷酸化。与此相反，外源性添加GM 3或LacCer拯救了被D-PdR预处理抑制的ERK 1/2的磷酸化。综上所述，这些结果表明，GM 3和LacCer是NT-4介导的Ambn表达所必需的，并有助于牙上皮细胞向成釉细胞分化。
Neurotrophin 4 (NT-4) and its receptors regulate the differentiation of ameloblasts in tooth development. Gangliosides, sialic acids that contain glycosphingolipids (GSLs), are involved in a variety of membrane-associated cell physiological functions such as ligand-receptor signal transmission. However, the expression patterns and functions of GSLs during tooth development remain unclear. In this study, we identified strong expressions of GM3 and LacCer in dental epithelium, which give rise to differentiation into enamel-secreting ameloblasts. Exogenous GM3 and LacCer in dental epithelial cells induced the expression ofameloblastin(Ambn), while it was also interesting that GM3 synergistically exerted enhancement of NT-4-mediatedAmbnexpression. In addition, consistently exogenous GM3 and LacCer in dental epithelial cells induced distinct activation of extracellular signal-regulated kinase 1/2 (ERK1/2), an event upstream of the expression ofAmbn.Furthermore, depletion of GSLs from dental epithelial cells by D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) inhibitedAmbnexpression as well as phosphorylation of ERK1/2. In contrast, exogenous addition of GM3 or LacCer rescued the phosphorylation of ERK1/2 repressed by pre-treatment with D-PDMP. Taken together, these results suggest that GM3 and LacCer are essential for NT-4-mediatedAmbnexpression, and contribute to dental epithelial cell differentiation into ameloblasts.