Department of Veterinary Anatomy, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Rinku-Ourai-Kita, Izumisano, Osaka 598-8531, Japan.
Histochem Cell Biol. 2011 Dec;136(6):617-36. doi: 10.1007/s00418-011-0867-2. Epub 2011 Sep 30.
Eph receptors and ephrin ligands are membrane-bound cell-cell communication molecules with well-defined roles in development. However, their expression and functions in the gastric epithelium are virtually unknown. We detected several EphB receptors and ephrin-Bs in the gastric corpus mucosa of the adult rodent stomach by RT-PCR amplification. Immunostaining showed complementary expression patterns, with EphB receptors preferentially expressed in the deeper regions and ephrin-Bs in the superficial regions of the gastric units. EphB1, EphB2 and EphB3 are expressed in mucous neck, chief and parietal cells, respectively. In contrast, ephrin-B1 is in pit cells and proliferating cells of the isthmus. In a mouse ulcer model, EphB2 expression was upregulated in the regenerating epithelium and expanded into the isthmus. Thus, EphB/ephrin-B signaling likely occurs preferentially in the isthmus, where receptor-ligand overlap is highest. We show that EphB signaling in primary gastric epithelial cells promotes cell retraction and repulsion at least in part through RhoA activation. Based on these findings, we propose that the EphB-positive progeny of gastric stem cells migrates from the isthmus toward the bottom of the gastric glands due to repulsive signals arising from contact with ephrin-Bs, which are preferentially expressed in the more superficial regions of the isthmus and gastric pits.
Eph 受体和 Ephrin 配体是膜结合的细胞间通讯分子，在发育过程中具有明确的作用。然而，它们在胃上皮中的表达和功能几乎未知。我们通过 RT-PCR 扩增检测到成年啮齿动物胃胃体黏膜中的几种 EphB 受体和 Ephrin-Bs。免疫染色显示互补的表达模式，EphB 受体优先表达在胃单位的较深区域，而 Ephrin-Bs 则表达在浅表区域。EphB1、EphB2 和 EphB3 分别在粘颈、主细胞和壁细胞中表达。相比之下，ephrin-B1 存在于 pit 细胞和峡部的增殖细胞中。在小鼠溃疡模型中，EphB2 在再生上皮中上调并扩展到峡部。因此，EphB/ephrin-B 信号可能优先发生在峡部，那里受体-配体的重叠最高。我们表明 EphB 信号在原代胃上皮细胞中促进细胞回缩和排斥，至少部分是通过 RhoA 激活。基于这些发现，我们提出胃干细胞的 EphB 阳性后代由于与 Ephrin-Bs 的接触而产生的排斥信号，从峡部向胃腺底部迁移，因为 Ephrin-Bs 优先表达在峡部和胃小凹的更浅表区域。
