Chemokine CXCL12 promotes the cross-talk between trophoblasts and decidual stromal cells in human first-trimester pregnancy
Chemokine CXCL12 promotes the cross-talk between trophoblasts and decidual stromal cells in human first-trimester pregnancy
复制标题
趋化因子 CXCL12 促进人类妊娠早期滋养层细胞和蜕膜基质细胞之间的相互作用。
DOI：
10.1093/humrep/den308
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发表时间：
2008-12-01
影响因子：
6.1
通讯作者：
Li, Da-Jin
中科院分区：
文献类型：
--
作者：
Zhou, Wen-Hui;Du, Mei-Rong;Li, Da-Jin
母胎对话的确切机制仍不清楚。为探讨趋化因子CXCL12及其受体CXCR4在滋养层细胞和蜕膜基质细胞(DSCs)相互作用中的作用，采用逆转录聚合酶链式反应和免疫组织化学方法检测CXCL12/CXCR4在滋养层细胞和DSCs中的表达。用酶联免疫吸附试验测定滋养层细胞分泌CXCL12的能力。采用细胞存活率实验、基质侵袭实验和酶谱分析CXCL12对滋养层细胞和DSCs生物学功能的影响。建立CXCL12/CXCR4共培养模型，研究CXCL12/CXCR4在滋养层细胞与DSC相互作用中的调控作用。体外培养的人滋养层细胞能自发分泌CXCL12，而DSCs则不能。CXCL12可显著增加滋养层细胞的侵袭力(P<；0.01)，并以自分泌和旁分泌的方式上调滋养层细胞和DSC的基质金属蛋白酶9(MMP9)和MMP2活性(均为P<；0.01)。与DSCs共培养后，滋养层细胞的侵袭力和MMP9、MMP2活性显著增加(P<0.01)，而抗CXCR4中和抗体可抑制这种作用。人滋养层细胞分泌的CXCL12通过调节MMP9和MMP2，增强滋养层细胞与DSCs之间的协同作用，从而改善母胎界面的功能。
The precise mechanisms in the materno-fetal dialogue still remain unclear. The aim of this study was to investigate the role of the chemokine CXCL12 and its receptor CXCR4 in the interaction of trophoblasts and decidual stromal cells (DSCs).Expression of CXCL12/CXCR4 in trophoblasts and DSCs was detected by reverse transcription-polymerase chain reaction and immunochemical staining. The secretion of CXCL12 by trophoblasts was determined by enzyme-linked immunosorbent assay. The effects of CXCL12 on the biological functions of trophoblasts and DSCs were analyzed using a cell viability assay, matrigel invasion assay and zymography. Finally, a co-culture model was established to investigate the modulation of CXCL12/CXCR4 in the interaction of trophoblasts and DSCs.CXCR4 was transcribed and translated by both human trophoblasts and DSCs. Human trophoblasts secreted CXCL12 spontaneously in vitro, but DSCs did not. CXCL12 induced an apparent increase in the invasiveness of trophoblasts (P < 0.01), and up-regulated matrix metalloproteinase (MMP) 9 and MMP2 activity of both trophoblasts and DSCs (both P < 0.01) in an autocrine and paracrine manner. The invasiveness and MMP9 and MMP2 activity of trophoblasts in co-culture with DSCs increased significantly (P < 0.01), and these could be inhibited by anti-CXCR4 neutralizing antibody.CXCL12 secreted by human trophoblasts enhances the coordination between trophoblasts and DSCs, via the regulation of MMP9 and MMP2, which may improve the functional materno-fetal interface.