The role of alpha(5)beta(1)-integrin in the IGF-I-induced migration of extravillous trophoblast cells during the process of implantation.
The role of alpha(5)beta(1)-integrin in the IGF-I-induced migration of extravillous trophoblast cells during the process of implantation.
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发表时间：
2004
影响因子：
4
通讯作者：
M. Kabir-Salmani;S. Shiokawa;Y. Akimoto;K. Sakai;M. Iwashita
中科院分区：
文献类型：
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作者：
M. Kabir-Salmani;S. Shiokawa;Y. Akimoto;K. Sakai;M. Iwashita
整合素在粘附和迁移过程中的作用使它们在胚胎植入和胎盘的复杂事件中有吸引力的潜在参与者。最近，α(v)β(3)-整合素通路在胰岛素样生长因子-I (IGF-I) 刺激的绒毛外滋养层 (EVT) 细胞迁移中发挥作用。本研究旨在研究α(5)β(1)-整合素在这方面的作用。使用培养的 EVT 细胞，在存在或不存在 GRGDSP 和 GRGESP 六肽、αIR3 以及针对 α(5)β(1)-整联蛋白的阻断抗体的情况下，对 IGF-I 处理或未处理的细胞进行迁移测定。采用免疫电子显微镜和免疫荧光染色来定位α(5)β(1)-和α(v)β(3)-整合素、Rab5a、桩蛋白、磷酸-FAK (pFAK) 和纽蛋白的分布。结果表明，用 GRGDSP 六肽、αIR3 和针对 α(5)β(1)-整合素的阻断抗体处理后，IGF-I 诱导的 EVT 细胞迁移被消除。此外，统计分析表明，核周区域中α(5)β(1)-整合素的面积相关数值密度显着高于细胞延伸区。免疫细胞化学实验表明，IGF-I 刺激的 EVT 细胞中 α(5)β(1)-整合素的内化率上调。此外，α(5)β(1)-整合素在EVT细胞的粘着斑处表现出与Rab5a共定位，但不与α(v)β(3)-整合素、pFAK、桩蛋白和纽蛋白共定位。总而言之，这些发现表明 α(5)β(1)-整合素在 IGF-I 促进的 EVT 细胞迁移中发挥重要作用。因此，IGF-I诱导的α(5)β(1)-整联蛋白内化可能是EVT细胞在着床和胎盘形成的复杂过程中迁移过程中的一个重要事件。
The role of integrins in the processes of adhesion and migration makes them attractive potential participants in the complex events of embryo implantation and placentation. Recently, the role of the alpha(v)beta(3)-integrin pathway was shown in the insulin-like growth factor-I (IGF-I)-stimulated migration of extravillous trophoblast (EVT) cells. This study was designed to investigate the role of alpha(5)beta(1)-integrin in this respect. Using cultured EVT cells, migration assays were carried out for IGF-I-treated or untreated cells in the presence or absence of the GRGDSP and GRGESP hexapeptides, alphaIR3, and a blocking antibody against alpha(5)beta(1)-integrin. Immuno-electron microscopy and immunofluorescent staining were performed to localize the distribution of alpha(5)beta(1)- and alpha(v)beta(3)-integrins, Rab5a, paxillin, phospho-FAK (pFAK), and vinculin. The results showed that IGF-I-induced migration of EVT cells was abolished following treatment with GRGDSP hexapeptide, alphaIR3, and a blocking antibody against alpha(5)beta(1)-integrin. Further, statistical analysis showed that the area-related numerical density of the alpha(5)beta(1)-integrin in the perinuclear regions was significantly higher than in the cell extensions. Immunocytochemical experiments demonstrated an up-regulation in internalization rate of alpha(5)beta(1)-integrin in IGF-I-stimulated EVT cells. Furthermore, alpha(5)beta(1)-integrin exhibited co-localization with Rab5a, but not with alpha(v)beta(3)-integrin, pFAK, paxillin, and vinculin at the focal adhesions of the EVT cells. Taken together, these findings suggest an essential role for alpha(5)beta(1)-integrin in IGF-I-promoted migration of EVT cells. It is possible therefore that IGF-I-induced internalization of alpha(5)beta(1)-integrin may be an important event during the migration of EVT cells in the complex processes of implantation and placentation.