Ephrin A1 induces intercellular dissociation in Ishikawa cells: possible implication of the Eph-ephrin A system in human embryo implantation
Ephrin A1 induces intercellular dissociation in Ishikawa cells: possible implication of the Eph-ephrin A system in human embryo implantation
复制标题
DOI：
10.1093/humrep/deq340
复制
发表时间：
2011-02-01
影响因子：
6.1
通讯作者：
Konishi, Ikuo
中科院分区：
文献类型：
--
作者：
Fujii, Haruko;Fujiwara, Hiroshi;Konishi, Ikuo
背景技术背景：在植入过程中，人类胚胎侵入子宫内膜间质组织，减少上皮细胞层之间的细胞间连接。由于Eph-ephrin相互作用可以诱导排斥力来控制细胞的位置和运动，我们研究了该系统可能参与子宫内膜上皮cells.METHODS：Eph A受体在人子宫内膜上皮细胞和子宫内膜癌源性石川细胞的表达通过RT-PCR，免疫组化和蛋白质印迹。Western blotting检测重组ephrin A1对石川细胞中Eph A2磷酸化的影响。结果：在人子宫内膜上皮细胞和石川细胞中检测到Eph A1、A2和A4 mRNA，在人囊胚中检测到Ephrin A1 mRNA。免疫组织化学染色显示Eph A1、A2和A4受体在增生期和分泌期子宫内膜的腔上皮和腺上皮细胞表面均有表达。蛋白质印迹分析证实Eph A2蛋白在人子宫内膜中的存在。重组ephrin A1与石川细胞结合，并诱导石川细胞中表达的Eph A2磷酸化。此外，刺激ephrin A1为20分钟增加单层石川细胞与对照cultures（P < 0.01）的渗透性，而不影响细胞violence.CONCLUSIONS：这项研究表明，Eph-ephrin A系统可以促进细胞间的解离在石川细胞表明在胚胎植入的初始步骤中的重要作用，通过打开子宫内膜上皮细胞屏障。
BACKGROUND: During implantation, the human embryo invades endometrial stromal tissues, reducing the intercellular connections among epithelial cell layers. Since Eph-ephrin interaction can induce repulsive forces to control cell position and movement, we examined the possible involvement of this system in intercellular dissociation among endometrial epithelial cells.METHODS: The expression of Eph A receptor on human endometrial epithelial cells and endometrial carcinoma-derived Ishikawa cells was examined by RT-PCR, immunohistochemistry and western blotting. The effects of recombinant ephrin A1 on Eph A2 phosphorylation in Ishikawa cells were also examined by western blotting. A permeability assay was performed to determine the effects of ephrin A1 on cell-to-cell adhesion.RESULTS: Eph A1, A2 and A4 mRNAs were detected in human endometrial epithelial cells and Ishikawa cells, and ephrin A1 was present in human blastocysts. Immunohistochemical staining showed that Eph A1, A2 and A4 receptors were expressed on the cell surface region of luminal and glandular epithelial cells in human endometrium in both the proliferative and secretory phase. The presence of Eph A2 protein in the human endometrium was confirmed by western blot analysis. Recombinant ephrin A1 was bound to Ishikawa cells and induced phosphorylation of Eph A2 expressed in Ishikawa cells. In addition, stimulation by ephrin A1 for 20 min increased the permeability of monolayer Ishikawa cells versus control cultures (P < 0.01), without affecting cell viability.CONCLUSIONS: This study demonstrated that the Eph-ephrin A system can promote intercellular dissociation in Ishikawa cells suggesting an important role in the initial step of embryo implantation by opening the endometrial epithelial cell barrier.