Regulation Of Sdf-1/cxcr7 On Trophoblasts Of Human First Trimester Gestation

Research Background Chemokines and chemokine receptors mediate the crosstalk between decidual immunocompetent cells(DIC) and trophoblasts, also are involved in the regulation of immunotolerance at materno-fetal interface. Among these, SDF-1/CXCR4 axis play an important role in recruiting peripheral CD56brightCD16-NK cells to deciduas and promoting invasion and proliferation of trophoblasts. Recently,RDC1 (CXCR7) was described as second receptor for CXCL12. CXCR7, a heptahelical receptor with strong phylogenetic similarity to GPCRs, was shown to bind CXCL12 and CXCL11 with high affinity, but fails to induce typical chemokine responses, such as cell migration and associated intracellular signal transduction. with CXCR7 identified as a new receptor for SDF-1, the role of the SDF-1-CXCR4 axis in regulating several biological processes becomes more complex. The function of CXCR7 is controversial. Some studies suggest a signaling activity in malignant mammalian cells and zebrafish embryos; expression of CXCR7 provides cells with a growth and survival advantage and increased adhesion properties. While others indicate to be a decoy activity or as a scavenger receptor. CXCR7 exerts effective capacity to eliminate CXCL12 from its surrounding environment. In this context, CXCR7 shows an anta-CXCR4 activity in the process of B cells maturation.Complex cytokine networks play an important role in a wide range of reproductive and pregnancy related processes. It has been demonstrated that Th2 polarization is beneficial for a successful pregnancy. Available reviews and our previous work have showed that chemokines could participate regulation of Th2 bias at materno-fetal interface. Inversely, cytokines could also affect expression of chemokines and chemokine receptors.Objectives Based on the research above, a detailed role for CXCR7 in differentiation and invasion of trophoblasts was explored, besides roles of SDF-1/CXCR4 axis. Also, affect of Th1/Th2-type cytokines on expression level of CXCR7,CXCR4 on trophoblasts was investigated.1. CXCR7 was expressed in villus and trophoblast cells of human first trimester gestation Methods:The villus were from women who had undergone an artificial abortion at 5-11 weeks of normal gestation for non medical cause. The total RNA was extracted by using the TRIzol reagent, from villus or the Percoll-gradient-isolated trophoblasts. The expression of chemokine receptors CXCR7 in the villus and Tro were investigated by way of semi-quantitative RT-PCR,immunohisochemistry and flow cytometer(FCS).Results:CXCR7 was expressed in villus and trophoblasts at both mRNA and protein level.Conclusion:Along with CXCR4, CXCR7 was expressed in trophoblasts, Considering 10 times more affinity with CXCR4, SDF-1/CXCR7 axis may play an important role in biological process of trophoblasts.2. Affect of Th1/Th2 cytokines on expression level of CXCR7,CXCR4 on trophoblastsMethods:The expression level of CXCR7,CXCR4 on trophoblasts was analyzed with FCS. The primary trophoblasts were treated in vitro with Thl- and Th2-type cytokines, TNFαand IL-10, respectively. The CXCR7,CXCR4 expression level was determined by flow cytometer(FCS).Results:Both CXCR7 and CXCR4 were significantly up-regulated by IL-10;While TNFαshowed no significant influence on expression level of CXCR7 and CXCR4.Conclusion:Along with CXCR4, CXCR7 was up-regulated significantly by IL-10; while TNFa had no such effect. Th2 bias cytokines may enhance biological functions of trophoblasts via SDF-1/CXCR4/CXCR7 axis.3. Roles of SDF-1/CXCR7 axis on proliferation and invasion of trophoblastsMethods:The trophoblasts were treated by different stimuli, including rhSDF-1, rhSDF-1+SDF-1 neutralizing antibodies, CXCR7,CXCR4 neutralizing antibodies respectively, CXCR7+ CXCR4 neutralizing antibodies. Then the viability and invasion of trophoblasts were detected respectively by MTT and Transwell assays.Results:Both CXCR7 and CXCR4 enhanced proliferation and invasion ability of trophoblasts.Conclusion:Both SDF-1/CXCR7 and SDF-1/CXCR4 signaling axis enhanced proliferation and invasion of trophoblasts. CXCR7 and CXCR4 would have synergistic effect on proliferation and invasion ability of trophoblasts.lt showed that CXCR7 could transduct active signaling or modulate CXCR4-signaling through heterodimerization with CXCR4.