Dynamic alterations in integrin α4 expression by hypoxia are involved in trophoblast invasion during early implantation
Dynamic alterations in integrin α4 expression by hypoxia are involved in trophoblast invasion during early implantation
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DOI：
10.1002/jcb.23398
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发表时间：
2012-02-01
影响因子：
4
通讯作者：
Kim, Gi-Jin
中科院分区：
文献类型：
--
作者：
Na, Kyu-Hwan;Lee, Hyun-Jung;Kim, Gi-Jin
囊胚植入母体子宫内膜是由胎盘的一群高度分化的原代细胞（称为滋养层细胞）介导的，这些细胞以类似于肿瘤细胞的侵袭性和破坏性方式生长。子宫内膜和滋养层细胞之间的相互作用受到侵入性绒毛外滋养层细胞分泌的细胞外基质（ECM）蛋白的协同相互作用的调节。整合素作为黏附受体，介导细胞 - 细胞外基质以及细胞 - 细胞之间的相互作用。然而，缺氧条件下整合素表达与滋养层细胞侵袭之间的相关性尚不清楚。在此，我们分析了在缺氧条件下HTR - 8/SVneo滋养层细胞中整合素的表达，以证明滋养层细胞的侵袭活性与整合素表达之间的关联。在1%缺氧处理后，通过微阵列分析、逆转录 - 聚合酶链反应、蛋白质印迹和酶谱分析对滋养层细胞进行检测，并评估细胞侵袭情况。在缺氧条件下观察到整合素和人基质金属蛋白酶（MMPs）的动态表达。通过MMP - 2和 - 9的改变，在1%缺氧条件下培养的滋养层细胞的侵袭性明显大于在常氧条件下培养的滋养层细胞的侵袭性（P
Implantation of the blastocyst into the maternal endometrium is mediated by a population of well-differentiated primary cells of the placenta known as trophoblasts, which grow in an invasive and destructive fashion similar to tumor cells. Interactions between the endometrium and trophoblasts are regulated by a coordinated interplay of extracellular matrix (ECM) proteins secreted by the invading extravillous trophoblasts. Integrins act as adhesion receptors and mediate both cellECM and cellcell interactions. However, the correlation between integrin expression and trophoblast invasion under hypoxia is unclear. Here, we analyzed the expression of integrins in HTR-8/SVneo trophoblast cells exposed to hypoxic conditions in order to demonstrate an association between invasion activity and integrin expression in trophoblasts. Trophoblasts were examined by microarray analysis, RT-PCR, western blotting, and zymography after 1% hypoxic treatment, and cell invasion was estimated. The dynamic expression of integrins and human matrix metalloproteinases (MMPs) was observed under hypoxic conditions. The invasiveness of trophoblasts cultured under 1% hypoxic conditions was significantly greater than that of trophoblasts cultured under normoxic conditions through alterations in MMP-2 and -9 (P