Goldenring J R, Poulsom R, Ray G S, Wright N, Meise K S, Coffey R J
Department of Medicine, Institute for Molecular Medicine and Genetics, Medical College of Georgia, Augusta 30912, USA.
Growth Factors. 1996;13(1-2):111-9. doi: 10.3109/08977199609034571.
Overexpression of transforming growth factor-alpha (TGF-alpha) in the gastric mucosa of metallothionein-TGF alpha (MT-TGF alpha) transgenic mice leads to a marked alteration in the ontogeny of the fundic cellular lineages. Induction of the transgene leads to the over-production of mucous cells with a concomitant diminution in the development of parietal cell and chief cell lineages. We have sought to define more precisely the mucous cell lineages involved in the mucous cell hyperplasia in MT-TGF alpha mice by investigating the expression of trefoil peptides in MT-TGF alpha mice. MT-TGF alpha mice and their non-transgenic littermates were treated with cadmium sulfate beginning at 13 days of age. Animals were then sacrificed at intervals over the following 2 weeks and gastric mucosa was examined for expression of trefoil peptides and TGF alpha by immunohistochemistry and in situ hybridization. No TGF alpha mRNA expression could be demonstrated by in situ hybridization in non-transgenic mice. In MT-TGF alpha mice, in situ grains for TGF alpha mRNA were detected at the base of fundic glands in 13 day old animals, whereas the expression was observed more widely in the mucosa of older animals (28 days). TGF alpha immunoreactivity was observed in foveolar mucous cells and residual parietal cells in MT-TGF alpha mice at all ages. By in situ hybridization, pS2 mRNA was detected in the surface mucous cells in normal gastric mucosa. In MT-TGF alpha mice, pS2 mRNA was found throughout the expanded foveolar region. By in situ hybridization, spasmolytic peptide (SP) expression was observed in the region of the progenitor zone in both groups of mice. By immunohistochemistry, SP expression was noted in a broad band of mucous neck cells deep to the progenitor zone. No gastric expression of intestinal trefoil factor (ITF) was noted in either group of mice. The results demonstrate that the expansion of the foveolar mucous cell compartment in MT-TGF alpha mice is due to the hyperplasia of normal surface cells expressing their particular mucin-associated trefoil peptide, pS2.
金属硫蛋白 - 转化生长因子α（MT - TGFα）转基因小鼠胃黏膜中转化生长因子α（TGF - α）的过表达导致胃底细胞谱系个体发育的显著改变。转基因的诱导导致黏液细胞过度产生，同时壁细胞和主细胞谱系的发育减少。我们试图通过研究MT - TGFα小鼠中三叶肽的表达来更精确地定义参与MT - TGFα小鼠黏液细胞增生的黏液细胞谱系。从13日龄开始，用硫酸镉处理MT - TGFα小鼠及其非转基因同窝仔鼠。然后在接下来的2周内每隔一段时间处死动物，通过免疫组织化学和原位杂交检查胃黏膜中三叶肽和TGFα的表达。原位杂交在非转基因小鼠中未检测到TGFα mRNA表达。在MT - TGFα小鼠中，13日龄动物的胃底腺底部检测到TGFα mRNA的原位颗粒，而在年龄较大的动物（28日龄）的黏膜中观察到更广泛的表达。在所有年龄段的MT - TGFα小鼠的胃小凹黏液细胞和残余壁细胞中均观察到TGFα免疫反应性。通过原位杂交，在正常胃黏膜的表面黏液细胞中检测到pS2 mRNA。在MT - TGFα小鼠中，在整个扩张的胃小凹区域发现了pS2 mRNA。通过原位杂交，在两组小鼠的祖细胞区均观察到解痉肽（SP）表达。通过免疫组织化学，在祖细胞区深处的宽带状黏液颈细胞中注意到SP表达。两组小鼠均未观察到肠三叶因子（ITF）的胃表达。结果表明，MT - TGFα小鼠胃小凹黏液细胞区室的扩张是由于表达其特定黏蛋白相关三叶肽pS2的正常表面细胞增生所致。
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