Kanaka-Gantenbein C, Dicou E, Czernichow P, Scharfmann R
INSERM CJF 93-13, Hôpital Robert Debré, Paris, France.
Endocrinology. 1995 Jul;136(7):3154-62. doi: 10.1210/endo.136.7.7789343.
In vivo, the differentiation of pancreatic islet stem cells depends on unknown soluble factors produced by the mesenchyme surrounding these cells. We have previously demonstrated that, like some neuronal cells, different beta-cell lines express functional nerve growth factor (NGF) receptors and can respond to NGF by extending neurite-like processes. NGF receptors are also expressed in vivo in mature rat islets and early during development in pancreatic ductular cells, which represent putative beta-stem cells. In this study, we have further characterized an in vitro model of islet development and studied the expression of NGF receptors and its ligand in this model. We have demonstrated the expression of Trk-A messenger RNA coding for the high affinity NGF receptor in islet cells and the localization of Trk protein in both alpha- and beta-islet cells. Moreover, the cells, from which islet cells "bud," also express Trk-A. Furthermore, NGF is produced and secreted by the nonendocrine cells surrounding the islets, suggesting a possible paracrine mode of action of NGF on the adjacent islet cells. Finally, islet morphogenesis is significantly retarded in the presence of K252a, an inhibitor of the tyrosine kinase activity of the family of Trk receptors, suggesting an implication of the neurotrophin-neurotrophin receptor axis in islet development.
在体内，胰岛干细胞的分化取决于这些细胞周围间充质产生的未知可溶性因子。我们之前已经证明，与一些神经元细胞一样，不同的β细胞系表达功能性神经生长因子（NGF）受体，并且可以通过延伸类神经突来对NGF作出反应。NGF受体在成熟大鼠胰岛中以及在代表假定β干细胞的胰腺导管细胞发育早期也在体内表达。在本研究中，我们进一步对胰岛发育的体外模型进行了表征，并研究了该模型中NGF受体及其配体的表达。我们已经证明了编码高亲和力NGF受体的Trk - A信使核糖核酸在胰岛细胞中的表达以及Trk蛋白在α和β胰岛细胞中的定位。此外，胰岛细胞“出芽”的细胞也表达Trk - A。此外，NGF由胰岛周围的非内分泌细胞产生和分泌，这表明NGF对相邻胰岛细胞可能存在旁分泌作用模式。最后，在Trk受体家族酪氨酸激酶活性抑制剂K252a存在的情况下，胰岛形态发生显著延迟，这表明神经营养因子 - 神经营养因子受体轴在胰岛发育中起作用。
