Zhou Wen-Hui, Du Mei-Rong, Dong Lin, Yu Jing, Li Da-Jin
Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai MedicalCollege, Shanghai 200011, PR China.
Hum Reprod. 2008 Dec;23(12):2669-79. doi: 10.1093/humrep/den308. Epub 2008 Aug 6.
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.
母胎对话的确切机制仍不清楚。本研究旨在探讨趋化因子CXCL12及其受体CXCR4在滋养层细胞与蜕膜基质细胞(DSCs)相互作用中的作用。
采用逆转录-聚合酶链反应和免疫化学染色检测CXCL12/CXCR4在滋养层细胞和DSCs中的表达。通过酶联免疫吸附测定法测定滋养层细胞分泌CXCL12的情况。使用细胞活力测定、基质胶侵袭试验和酶谱分析来分析CXCL12对滋养层细胞和DSCs生物学功能的影响。最后,建立共培养模型以研究CXCL12/CXCR4在滋养层细胞与DSCs相互作用中的调节作用。
人滋养层细胞和DSCs均转录并翻译CXCR4。人滋养层细胞在体外自发分泌CXCL12,但DSCs不分泌。CXCL12以自分泌和旁分泌方式诱导滋养层细胞侵袭性明显增加(P < 0.01),并上调滋养层细胞和DSCs的基质金属蛋白酶(MMP)9和MMP2活性(均P < 0.01)。与DSCs共培养的滋养层细胞的侵袭性以及MMP9和MMP2活性显著增加(P < 0.01),且这些可被抗CXCR4中和抗体抑制。
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,这可能改善母胎功能界面。