Peters Katharina, Panienka Roswitha, Li Jinming, Klöppel Günter, Wang Rennian
Department of Pathology, University of Kiel, Kiel, Germany.
Virchows Arch. 2005 Jan;446(1):56-63. doi: 10.1007/s00428-004-1145-7. Epub 2004 Nov 30.
Ligation of the pancreatic duct has been shown to induce islet cell neogenesis from duct cells in the adult rat pancreas. The transcription factors that regulate islet cell neogenesis and the phenotype of putative precursor cells involved in neogenesis are unknown. We, therefore, studied the expression of the transcription factors Pdx1, Pbx1, Meis2, Nkx2.2 and the putative stem cell markers c-Kit and nestin in rat pancreata 3, 5 and 7 days after duct ligation. Immunocytochemical staining revealed a subpopulation of cells in the ligated portion of the pancreas that was positive for the putative stem cell markers c-Kit and nestin. The c-Kit immunoreactivity was upregulated, reaching a peak at day 3, while nestin expression peaked at day 7. The c-Kit-positive cells were located among the duct and islet cells, while nestin-expressing cells were found scattered in the duct epithelium at day 3 and around the ducts at day 7. Both c-Kit- and nestin-positive cells showed high proliferative activity, as determined by BrdU labeling. Pdx1 and Nkx2.2 were found predominantly in the duct cells of the ligated pancreas. There were significant changes in the expression patterns of Pbx1 and Meis2 in the ductular complexes. The findings indicate that the stem cell markers c-Kit and nestin as well as the transcription factors Pdx1 and Nkx2.2 are upregulated in compartments of the pancreas that are involved in islet cell neogenesis after duct ligation.
胰腺导管结扎已被证明可诱导成年大鼠胰腺导管细胞产生胰岛细胞新生。调节胰岛细胞新生的转录因子以及参与新生的假定前体细胞的表型尚不清楚。因此，我们研究了胰腺导管结扎后3天、5天和7天大鼠胰腺中转录因子Pdx1、Pbx1、Meis2、Nkx2.2以及假定干细胞标志物c-Kit和巢蛋白的表达。免疫细胞化学染色显示，胰腺结扎部分存在一群细胞，它们对假定干细胞标志物c-Kit和巢蛋白呈阳性。c-Kit免疫反应性上调，在第3天达到峰值，而巢蛋白表达在第7天达到峰值。c-Kit阳性细胞位于导管和胰岛细胞之间，而表达巢蛋白的细胞在第3天分散在导管上皮中，在第7天位于导管周围。通过BrdU标记确定，c-Kit和巢蛋白阳性细胞均显示出高增殖活性。Pdx1和Nkx2.2主要存在于结扎胰腺的导管细胞中。导管复合体中Pbx1和Meis2的表达模式有显著变化。这些发现表明，在胰腺导管结扎后参与胰岛细胞新生的区域，干细胞标志物c-Kit和巢蛋白以及转录因子Pdx1和Nkx2.2上调。
