Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Av Prof Lineu Prestes 1524 ICB I 05508-900 São Paulo, SP, Brazil.
Differentiation. 2010 Jan;79(1):48-56. doi: 10.1016/j.diff.2009.09.001. Epub 2009 Sep 24.
The development of the gastric mucosa is controlled by hormones, growth factors and feeding behavior. Early weaning (EW), which means the abrupt interruption of suckling, increases proliferation and differentiation in the rat gastric epithelium. Transforming growth factor alpha (TGFalpha) is secreted in the stomach, binds to the epidermal growth factor receptor (EGFR) and may control cell proliferation, differentiation and migration. Here, we investigated the influence of suckling-weaning transition on the differentiation of mucous neck cells in the stomach and its association to the expression of TGFalpha and EGFR. Fifteen-day-old Wistar rats were divided into two groups: suckling (control), in which pups were kept with the dam, and early weaning (EW), in which rats were separated from their mother and fed with hydrated powdered chow. TGFalpha and EGFR levels were increased at 18 days in EW animals compared to control ones (p<0.05). Histochemical reactions with Periodic Acid-Schiff reagent+Alcian Blue or Bandeiraea simplicifolia II lectin were used to stain the mucous neck cells and showed an increase in this cell population throughout EW, which was more pronounced at 17 days when compared to suckling pups (p<0.05). These morphological results were confirmed by RT-PCR for mucin 6. The levels of mucin 6 mRNA were higher in EW animals from the 16th to the 18th day (1-3 days post-weaning) when compared to the respective control group. Inhibition of EGFR through AG1478 administration to EW animals prevented the expansion of mucous neck cell population induced by EW (p<0.05). Therefore, early weaning up regulated TGFalpha/EGFR expression and induced differentiation of mucous neck cells. Moreover, we showed that EGFR takes part in the maturation of this cell population. We conclude that regular suckling-weaning transition is crucial to guarantee the development of the gastric mucosa.
胃黏膜的发育受激素、生长因子和喂养行为的控制。早期断奶（EW），即突然中断哺乳，会增加大鼠胃上皮的增殖和分化。转化生长因子 alpha（TGFalpha）在胃中分泌，与表皮生长因子受体（EGFR）结合，可能控制细胞增殖、分化和迁移。在这里，我们研究了哺乳-断奶过渡期对胃黏膜黏液颈细胞分化的影响及其与 TGFalpha 和 EGFR 表达的关系。将 15 日龄 Wistar 大鼠分为两组：哺乳（对照），将幼仔留在母鼠身边；早期断奶（EW），将大鼠与母鼠分离并喂食水合粉末饲料。与对照组相比，EW 动物在 18 天时 TGFalpha 和 EGFR 水平升高（p<0.05）。用过碘酸-Schiff 试剂+阿尔辛蓝或 Bandeiraea simplicifolia II 凝集素的组织化学反应染色黏液颈细胞，显示该细胞群体在整个 EW 期间增加，与哺乳幼仔相比，17 天时更为明显（p<0.05）。这些形态学结果通过 MUC6 的 RT-PCR 得到证实。与相应的对照组相比，EW 动物的 MUC6 mRNA 水平在 16 至 18 天（断奶后 1-3 天）时更高。通过向 EW 动物施用 AG1478 抑制 EGFR，可防止 EW 诱导的黏液颈细胞群体扩张（p<0.05）。因此，早期断奶上调了 TGFalpha/EGFR 的表达，并诱导了黏液颈细胞的分化。此外，我们表明 EGFR 参与了该细胞群体的成熟。我们得出结论，规律的哺乳-断奶过渡对于保证胃黏膜的发育至关重要。
