FIG. 9.

β3-endonexin deficiency promotes the angiogenic response in vivo. (A) HMEC-1 cells were transfected with an expression vector for β3-endonexin long (EN-L) or control vector (Ctr), seeded on matrigel, and exposed to VEGF (1 μg/μl) for 6 h or remained untreated (Ctr). A representative figure is shown (n=3). (B) HMEC-1 cells transfected with RNAi against β3-endonexin (siEN) or with scrambled RNA (siCtr) were mixed with matrigel. Plugs were injected subcutaneously in mice and excised after 7 days. Immunohistochemistry was performed with an antibody against CD31 to stain for human endothelial cells. Representative figures are shown (n=3, *p<0.05 vs. siCtr). (C) Under hypoxic conditions, NFκB subunits p50 and p65 bind to the HIF-1α promoter, thereby maintaining HIF-1α transcription. Subsequently, β3-endonexin translocates to the nucleus and prevents NFκB binding to the HIF-1α promoter at the NFκB-binding site (NFκB BS) by complexing p50 and p65, thus resulting in decreased HIF-1α mRNA levels.