Effect of CXCL12/CXCR4 on migration of decidua-derived mesenchymal stem cells from pregnancies with preeclampsia
Effect of CXCL12/CXCR4 on migration of decidua-derived mesenchymal stem cells from pregnancies with preeclampsia
复制标题
CXCL12/CXCR4对子痫前期妊娠蜕膜间充质干细胞迁移的影响
DOI：
10.1111/aji.13180
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发表时间：
2019-11-01
影响因子：
3.6
通讯作者：
Yu, Li-Li
中科院分区：
文献类型：
--
作者：
Lei, Guo-Qin;Wu, Zhi-Yu;Yu, Li-Li
问题：母体免疫失衡引起的全身性免疫炎症反应是子痫前期(PE)发病机制的核心。我们推测蜕膜间充质干细胞(DMSCs)数量的变化可能与母体免疫失衡有关。本研究旨在探讨CXCL12/CXCR4轴在PE患者中的表达及其对骨髓间充质干细胞迁移行为的影响，以进一步阐明PE的发病机制。采用II型胶原酶消化法和贴壁法从蜕膜组织中提取DMSCs。采用酶联免疫吸附试验和免疫组织化学方法检测血清和组织中CXCL12的表达水平。用Q-PCR和Western blotting检测DMSCs上CXCR4的表达，Transwell法检测dMSCs的迁移能力。结果：PE患者蜕膜间充质干细胞CXCR4和HIF-1α的表达均高于对照组。胎膜组织中CXCL12水平最高，其次是胎盘和脐带，而对照组组织中CXCL2水平在脐带中最高，其次是胎盘和蜕膜。在CXCL12的诱导下，PE患者蜕膜间充质干细胞的迁移能力可能高于正常对照的dMSCs，而在低氧环境下，dMSCs的迁移能力较常氧环境下有所下降。结论：PE患者的蜕膜间充质干细胞能够以CXCL12的浓度梯度向蜕膜层迁移，这可能在PE的发生发展中起一定作用。
Problem: Systemic immuno-inflammatory response caused by maternal immune imbalance is central to the pathogenesis of preeclampsia (PE). We hypothesized that changes in the number of decidual mesenchymal stem cells (dMSCs) may be associated with maternal immune imbalance. We aimed to evaluate the expression of CXCL12/CXCR4 axis in patients with PE and its influence on the migration behavior of dMSCs, to further clarify the pathogenesis of PE.Method of study: Fourteen women with PE and 11 controls were included. DMSCs were extracted from decidual tissue by type II collagenase digestion and adherence. ELISA and immunohistochemistry analysis were used to measure serum and tissue levels of CXCL12. Q-PCR and Western blotting were used to detect CXCR4 expression on dMSCs, whereas transwell assay was used to measure the migration ability of dMSCs.Results: Decidual mesenchymal stem cells from women with PE showed higher expressions of CXCR4 and HIF-1 alpha than the dMSCs of controls did. Tissues from women with PE showed the highest CXCL12 levels in the decidua, followed by the placenta and umbilical cord, whereas tissues from controls showed the highest CXCL2 levels in the umbilical cord, followed by the placenta and decidua. dMSCs from women with PE showed possibly higher migration ability than that of dMSCs from controls, under the induction of CXCL12, whereas dMSCs showed a decreasing trend in hypoxic than in normoxic environment.Conclusion: Decidual mesenchymal stem cells from women with PE can migrate to the decidua layer with the concentration gradient of CXCL12, which may play a role in the occurrence and development of PE.