Signaling through fibroblast growth factor receptor 2b plays a key role in the development of the exocrine pancreas
Signaling through fibroblast growth factor receptor 2b plays a key role in the development of the exocrine pancreas
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DOI：
10.1073/pnas.96.11.6267
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发表时间：
1999-05-25
影响因子：
11.1
通讯作者：
Scharfmann, R
中科院分区：
文献类型：
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作者：
Miralles, F;Czernichow, P;Scharfmann, R
胰腺的发育依赖于上皮-间充质的相互作用。成纤维细胞生长因子(FGFs)及其受体(FGFR1-4)被认为是不同器官上皮-间充质相互作用的介质。我们在这里显示FGFR-2 IIIb及其配体成纤维细胞生长因子-1、成纤维细胞生长因子-7和成纤维细胞生长因子-10在整个胰腺发育过程中都有表达。我们还发现，在无间充质培养的胚胎胰腺上皮细胞中，成纤维细胞生长因子-1、成纤维细胞生长因子-7和成纤维细胞生长因子-IO能刺激胰腺外分泌细胞的生长、形态发生和细胞分化。通过使用反义FGFR-2 IIIb寡核苷酸或可溶性重组FGFR-2 IIIb蛋白抑制FGFR-2 IIIb信号，进一步研究FGFs通过FGFR-2 IIIb信号转导的作用。取消FGFR-2 IIIb信号导致外植体的大小显著减小，外分泌细胞的发育减少了2倍。这些结果表明，FGFs通过FGFR-2 IIIb信号通路在胰腺外分泌发育中起重要作用。
The development of the pancreas depends on epithelial-mesenchymal interactions. Fibroblast growth factors (FGFs) and their receptors (FGFRs 1-4) have been identified as mediators of epithelial-mesenchymal interactions in different organs. We show here that FGFR-2 IIIb and its ligands FGF-1, FGF-7, and FGF-10 are expressed throughout pancreatic development. We also show that in mesenchyme-free cultures of embryonic pancreatic epithelium FGF-1, FGF-7, and FGF-IO stimulate the growth, morphogenesis, and cytodifferentiation of the exocrine cells of the pancreas. The role of FGFs signaling through FGFR-2 IIIb was further investigated by inhibiting FGFR-2 IIIb signaling in organocultures of pancreatic explants (epithelium + mesenchyme) by using either antisense FGFR-2 IIIb oligonucleotides or a soluble recombinant FGFR-2 IIIb protein. Abrogation of FGFR-2 IIIb signaling resulted in a considerable reduction in the size of the explants and in a 2-fold reduction of the development of the exocrine cells. These results demonstrate that FGFs signaling through FGFR-2 IIIb play an important role in the development of the exocrine pancreas.