Effects of Fibronectin, VEGF and Angiostatin on the expression of MMPs through different signaling pathways in the JEG-3 cells

Problem: The objective of this study was to evaluate the possible signal pathway of fibronectin (FN), vascular endothelial growth factor (VEGF) and angiostatin (AS) on the expression of matrix metalloproteinases (MMPs) in JEG-3 cells. Methods of study: JEG-3 cells were cultured and were examined for the effect of FN, VEGF and AS on the expression of MMPs by immunocytochemistry, gelatin zymography, Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR). Results: We found that up-regulation of the expression of MMPs was induced by FN and VEGF through the focal adhesion kinase (FAK)/mitogen-activated protein kinase (MAPK) and Flt-1/p38^SAPK/ MAPKAPK2 signaling pathways, respectively. Furthermore, AS down-regulated the expression of MMPs through the integrin αVβ3/ FAK signaling pathway independent of the integrin-binding motif Arg-Gly-Asp (RGD). Conclusion: These data indicate that the expression of MMPs is regulated by many independent factors (such as FN, VEGF and AS) through different signaling pathways which influence the behavior of trophoblast cells.