Figure 7.

Schematic diagram showing a dual role of ADAM9 in angiogenesis regulation through its protease activity and transcriptional regulation in nucleus. The protease function of ADAM9 increases PLAT expression for extracellular matrix degradation and proangiogenesis. In hypoxia, nuclear translocation of ADAM9 is increased and nuclear ADAM9 occupies the promoters of SERPINE1 and PGK1, leading to transcriptional repression of SERPINE1 and PGK1 for reducing angiostatin formation and thus promoting angiogenesis.