Signal Transduction and Transcriptional Regulation of Angiogenesis

摘要: When quiescent endothelial cells (ECs) are exposed to angiogenic factor such as VEGF,* ECs express proteases degrade extracellular matrices, migrate, proliferate and form new vessels. However, the molecular mechanism of these events is not fully characterized yet. We studying signal transduction transcriptional regulation angiogenesis. investigated properties two VEGF receptors, Flt-1 KDR, by using newly developed blocking monoclonal antibodies (mAbs), i.e., anti-human mAb antihuman KDR mAb. elicited induction transcription Ets-1 in human umbilical vein (HUVECs). This was mediated KDR/Flt-1 heterodimer homodimer. The role angiogenesis further clarified. established both high low expressing EC lines, compared cell lines with a parental murine line, MSS31. growth rate almost identical among three lines. It appeared that gene expressions matrix metalloproteinases (MMP-1, MMP-3, MMP-9) well integrin beta3 were correlated level expression. As result, invasiveness enhanced reduced cells, made more tube-like structures type 1 collagen gel. These results indicate principle converting angiogeneic phenotype.