Complementary expression and repulsive signaling suggest that EphB receptors and ephrin-B ligands control cell positioning in the gastric epithelium
Complementary expression and repulsive signaling suggest that EphB receptors and ephrin-B ligands control cell positioning in the gastric epithelium
复制标题
DOI：
10.1007/s00418-011-0867-2
复制
发表时间：
2011-12-01
影响因子：
2.3
通讯作者：
Nakajima, Takayuki
中科院分区：
文献类型：
--
作者：
Ogawa, Kazushige;Takemoto, Natsuki;Nakajima, Takayuki
Eph受体和Eaffin配体是膜结合的细胞-细胞通讯分子，在发育过程中发挥着明确的作用。然而，它们在胃上皮细胞中的表达和功能几乎是未知的。通过RT-PCR扩增，在成年啮齿动物胃体粘膜中检测到多种EphB受体和Ephin-B。免疫组织化学染色呈互补表达模式，EphB受体优先表达于胃单位深层，Ephin-B受体优先表达于胃单位浅表区域。EphB1、EphB2和EphB3分别在颈部粘液细胞、主细胞和壁细胞中表达。与之相反的是，在峡部的凹陷细胞和增殖细胞中有eaffin-B1的表达。在小鼠溃疡模型中，EphB2在再生的上皮细胞中表达上调，并扩展到峡部。因此，EphB/ePhin-B信号可能优先发生在受体-配体重叠最高的峡部。我们发现原代胃上皮细胞中的EphB信号促进了细胞的回缩和排斥，至少部分是通过RhoA的激活。基于这些发现，我们推测EphB阳性的胃干细胞后代由于与Ephin-B接触而产生的排斥信号而从峡部向胃腺底部迁移，这些信号优先表达于峡部和胃小窝的更浅的区域。
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.