CX3CL1 and CCL14 regulate extracellular matrix and adhesion molecules in the trophoblast: Potential roles in human embryo implantation
CX3CL1 and CCL14 regulate extracellular matrix and adhesion molecules in the trophoblast: Potential roles in human embryo implantation
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DOI：
10.1095/biolreprod.107.066480
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发表时间：
2008-07-01
影响因子：
3.6
通讯作者：
Salamonsen, Lois A.
中科院分区：
文献类型：
--
作者：
Hannan, Natalie J.;Salamonsen, Lois A.
胚胎着床是一个涉及囊胚的复杂过程。附着于子宫内膜上皮和随后的滋养细胞浸润蜕膜。我们之前的研究表明，趋化因子CX3CR1和CCL14此时在子宫内膜血管、上皮细胞和蜕膜细胞中含量丰富，它们的受体CX3CR1和CCR1存在于入侵的人滋养细胞上。CX3CL1和CCL14促进滋养细胞迁移。我们假设这些子宫内膜趋化因子通过调节滋养细胞上的粘附分子和细胞外基质（ECM）成分来促进滋养细胞迁移，类似于白细胞运输中使用的机制。先前使用的滋养细胞（AC1M-88）在CX3CL1和CCL14处理后，对纤维连接蛋白的粘附明显增加。使用通路特异性寡核苷酸阵列和实时定量RTPCR检测趋化因子刺激后滋养细胞粘附和ECM的变化。CX3CL1处理影响了30多个基因，CCL14处理调节了15个基因。Real-time RT-PCR结果显示，趋化因子处理后，α -catenin （CTNNA1）、细胞外基质蛋白1 （ECMI）、骨桥蛋白（SPP1）、整合素α 6 （ITGA6）、基质金属蛋白酶12 （MMP12）和整合素β 5 (ITGB5) mRNA转录本发生了显著变化。这些基因中的一些先前与着床有关。免疫组织化学证实在妊娠早期植入部位存在整合素α 6和SPP1蛋白。趋化因子及其受体、黏附和母胎界面ECM的时空表达强调了滋养细胞通过母体蜕膜定向迁移的重要作用。本研究首次证实了CX3CL1和CCL14对滋养层粘附分子和ECM的直接影响，提示了滋养层细胞在妊娠早期迁移的机制。
Embryo implantation is a complex process involving blastocyst. attachment to the endometrial epithelium and subsequent trophoblast invasion of the decidua. We have previously shown that the chemokines CX3CL1 and CCL14 are abundant in endometrial vasculature, epithelial, and decidual cells at this time, and that their receptors, CX3CR1 and CCR1, are present on invading human trophoblasts. CX3CL1 and CCL14 promote trophoblast migration. We hypothesized that these endometrial chemokines promote trophoblast migration by regulating adhesion molecules and extracellular matrix (ECM) components on the trophoblast, similar to mechanisms used in leukocyte trafficking. Trophoblast cells (AC1M-88) used previously showed a marked increase in adhesion to fibronectin following treatment with CX3CL1 and CCL14. Alterations in trophoblast adhesion and ECM following chemokine stimulation were examined using pathway-specific oligo-arrays and quantitative real-time RTPCR. More than 30 genes were affected by CX3CL1 treatment, and 15 genes were found to be regulated by CCL14 treatment. Real-time RT-PCR quantitation revealed significant changes in the mRNA transcripts of alpha-catenin (CTNNA1), extracellular matrix protein 1 (ECMI), osteopontin (SPP1), integrin alpha 6 (ITGA6), matrix metalloproteinase 12 (MMP12), and integrin beta 5 (ITGB5) following chemokine treatment. Several of these genes have previously been implicated in implantation. Immunohistochemistry confirmed the presence of integrin alpha 6 and SPP1 protein in first-trimester human implantation sites. The temporal and spatial expression of chemokines, their receptors, adhesion, and ECM at the maternal-fetal interface emphasizes an important role in the controlled directional migration of trophoblasts through the maternal decidua. For the first time, this study demonstrates the direct effects of CX3CL1 and CCL14 on trophoblast adhesion molecules and ECM, suggesting mechanisms by which trophoblast cells migrate during early pregnancy.