XCL1-XCR1 pathway promotes trophoblast invasion at maternal-fetal interface by inducing MMP-2/MMP-9 activity

ProblemCertain chemokines with their receptors can promote or inhibit trophoblast cell migration and invasion in human first-trimester placenta. Whether the lymphotactin (Lptn; XCL1)XC chemokine receptor 1 (XCR1) chemokine pathway affects trophoblast cell migration and invasion in human first-trimester placenta remains unclear. Method of studyThe expression pattern of chemokine XCL1 and its receptor XCR1 was detected in human first-trimester by qRT-PCR, and the effect of recombinant human XCL1 (rhXCL1) on trophoblast cell function was tested by wound healing and Transwell assays. Matrix metalloproteinase (MMP) activity in trophoblast cells treated with rhXCL1 was assessed via qRT-PCR and gelatin zymography. ResultsAbundant XCR1 mRNA was expressed in the first-trimester decidua and villi. XCL1 and XCR1 mRNA were expressed at a higher level in the first-trimester than in the term placenta. RhXCL1 promoted trophoblast cell migration and invasion by increasing MMP-9 and MMP-2 activity and that of the MMP-2/tissue inhibitor of metalloproteinases 2 (TIMP-2) complex via the phosphatidylinositol 3-kinase (PI3K)/AKT kinase (AKT), mitogen-activated protein kinase (MEK), and JUN N-terminal kinase (JNK) signaling pathways. ConclusionXCL1-XCR1 chemokine pathway promotes trophoblast invasion by increasing matrix metalloproteinase activity in human first-trimester placenta.