Nestin expression in pancreatic endocrine and exocrine cells of mice lacking glucagon signaling

Nestin expression in pancreatic endocrine and exocrine cells of mice lacking glucagon signaling
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DOI:
10.1002/dvdy.21112
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发表时间:
2007-04-01
影响因子:
2.5
通讯作者:
Teitelman, Gladys
Teitelman, Gladys
中科院分区:
生物学3区
文献类型:
--
作者:
Kedees, Mamdouh H.;Guz, Yelena;Teitelman, Gladys

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神经干细胞的标记物巢蛋白也由位于胰腺原基上皮中的细胞和外分泌细胞亚群表达,但不由内分泌细胞表达。这些发现提出了这样的可能性,即胰腺上皮是异质的,并且由外分泌/巢蛋白阳性和内分泌/巢蛋白阴性前体细胞的亚群组成。我们在两个突变小鼠模型中研究了这个问题,其特征在于胰岛细胞中几种胚胎特性的长期表达。一个突变系包括由于前蛋白转化酶-2(PC 2(-/-))的消除而缺乏成熟胰高血糖素的小鼠,前蛋白转化酶-2负责将胰高血糖素原转化为胰高血糖素,而第二个系由胰高血糖素受体(Gegr(-/-))整体缺失的小鼠组成。我们证明,巢蛋白是瞬时表达的腺泡细胞和胰岛素和胰高血糖素细胞的胰岛的两个线的小鼠。此外,胰高血糖素信号的缺乏增加了突变胚胎和成年小鼠胰腺中巢蛋白mRNA的水平。我们得出结论,巢蛋白+细胞位于胰腺原基产生的细胞的内分泌和外分泌谱系。此外,我们的研究结果表明,巢蛋白的表达受胰高血糖素信号。
Nestin, a marker of neural stem cells, is also expressed by cells located in the epithelium of the pancreatic primordium and by a subpopulation of exocrine cells but not by endocrine cells. These findings raised the possibility that the pancreatic epithelium is heterogeneous and comprised of subpopulations of exocrine/ nestin-positive and endocrine/nestin-negative precursor cells. We examined this issue in two mutant mouse models characterized by protracted expression of several embryonal properties in islet cells. One mutant line comprises mice lacking mature glucagon due to abrogation of proprotein convertase-2 (PC2(-/-)), responsible for the conversion of proglucagon into glucagon, while the second line consists of mice with a global deletion of the glucagon receptor (Gegr(-/-)). We demonstrate that nestin is transiently expressed by acinar cells and by insulin and glucagon cells of islets of both lines of mice. In addition, the lack of glucagon signaling increased nestin mRNA levels in pancreas of mutant embryos and adult mice. We conclude that nestin+ cells located in the pancreatic primordium generate the cells of the endocrine and exocrine lineages. Furthermore, our results suggest that nestin expression is regulated by glucagon signaling.