Miralles F, Czernichow P, Scharfmann R
INSERM U457, Hospital Robert Debré, 48, Boulevard Sérurier, 75019 Paris, France.
J Endocrinol. 1999 Mar;160(3):433-42. doi: 10.1677/joe.0.1600433.
The factors regulating the differentiation of the endocrine cells of the pancreas are still unknown. In previous studies, we have demonstrated that, like neurones, various beta-cell lines express functional neurotrophin receptors. Moreover, Trk-A, the nerve growth factor (NGF) high-affinity receptor, is expressed in vivo in mature rat islets and early during development in the pancreatic ductal network that represents the source of putative stem cells. Rat pancreatic AR42J cells possess both exocrine and neuroendocrine properties. Recent studies have shown that these cells can differentiate either into acinar cells or into insulin-expressing cells. In this study, we demonstrate that AR42J cells, in common with the embryonic ductal cells, do express Trk-A. Moreover, on treatment with NGF, Trk-A is phosphorylated and early responsive genes such as NGFI-A, c-fos and c-jun are induced. These results clearly show that the Trk-A receptor expressed in AR42J is functional. AR42J cells provide a model system with which to study the role of NGF in the development of the pancreatic cells.
调节胰腺内分泌细胞分化的因素仍然未知。在先前的研究中,我们已经证明,与神经元一样,各种β细胞系表达功能性神经营养因子受体。此外,神经生长因子(NGF)的高亲和力受体Trk-A在成熟大鼠胰岛中以及在代表假定干细胞来源的胰腺导管网络发育早期在体内表达。大鼠胰腺AR42J细胞具有外分泌和神经内分泌特性。最近的研究表明,这些细胞可以分化为腺泡细胞或表达胰岛素的细胞。在本研究中,我们证明AR42J细胞与胚胎导管细胞一样,确实表达Trk-A。此外,用NGF处理后,Trk-A被磷酸化,并且诱导早期反应基因如NGFI-A、c-fos和c-jun。这些结果清楚地表明AR42J中表达的Trk-A受体是有功能的。AR42J细胞提供了一个模型系统,用以研究NGF在胰腺细胞发育中的作用。