Kanaka-Gantenbein C, Tazi A, Czernichow P, Scharfmann R
INSERM CJF 9313, Hôpital Robert Debré, Paris, France.
Endocrinology. 1995 Feb;136(2):761-9. doi: 10.1210/endo.136.2.7835308.
It is now established that the pancreatic islet cells derive from precursors present in the pancreatic ducts. These precursor cells as well as the factors that influence their differentiation to mature insulin-secreting beta-islet cells are nevertheless not elucidated yet. However, the large number of similarities existing between beta-cells and neuronal cells led to the suggestion that these two different cell types may be sensitive to the same growth and differentiation factors, for example, nerve growth factor (NGF), which is important for the differentiation and survival of several neurons. It was previously demonstrated that the high affinity NGF receptor, Trk-A, which is sufficient for NGF signal transduction, is expressed in different beta-cell lines and in normal rat islet cells in primary culture. The aim of this study was therefore to examine whether the Trk-A receptor is present in vivo in the rat pancreas during development and in adult life. By double immunofluorescence analysis using anti-Trk-A/antiinsulin or anti-Trk-A/antiglucagon antibodies on pancreatic sections of adult rats, it is demonstrated that the Trk-A protein is present in the beta- and not in the alpha-islet cells of adult rat pancreas. No Trk-A immunostaining was observed in the exocrine pancreas or in the pancreatic ducts of adult pancreas. Interestingly, the pattern of Trk-A immunolocalization in the pancreas is different during fetal life, when Trk-A immunostaining is observed in the pancreatic ductular cells and undetectable in both beta- and alpha-islet cells. During late prenatal and early postnatal life, Trk-A immunostaining is present in the islet cells, although weaker than in adult rats, and progressively decreases in the pancreatic ducts, as pancreatic maturation progresses. The intensity and localization of the Trk-A immunostaining in the rat pancreas are therefore developmentally regulated.
现已确定，胰岛细胞源自胰腺导管中存在的前体细胞。然而，这些前体细胞以及影响它们分化为成熟胰岛素分泌β胰岛细胞的因素尚未阐明。然而，β细胞和神经元细胞之间存在大量相似之处，这表明这两种不同的细胞类型可能对相同的生长和分化因子敏感，例如神经生长因子（NGF），它对几种神经元的分化和存活很重要。先前已证明，高亲和力NGF受体Trk-A足以进行NGF信号转导，在不同的β细胞系和原代培养的正常大鼠胰岛细胞中表达。因此，本研究的目的是检查Trk-A受体在大鼠胰腺发育过程中和成年期是否存在于体内。通过在成年大鼠胰腺切片上使用抗Trk-A/抗胰岛素或抗Trk-A/抗胰高血糖素抗体进行双重免疫荧光分析，证明Trk-A蛋白存在于成年大鼠胰腺的β胰岛细胞中，而不存在于α胰岛细胞中。在成年胰腺的外分泌胰腺或胰腺导管中未观察到Trk-A免疫染色。有趣的是，在胎儿期，胰腺中Trk-A免疫定位的模式不同，此时在胰腺导管细胞中观察到Trk-A免疫染色，而在β和α胰岛细胞中均未检测到。在产前后期和产后早期，Trk-A免疫染色存在于胰岛细胞中，尽管比成年大鼠弱，并且随着胰腺成熟的进展，在胰腺导管中逐渐减少。因此，大鼠胰腺中Trk-A免疫染色的强度和定位受发育调控。
