VEGF-Induced Endothelial Podosomes via ROCK2-Dependent Thrombomodulin Expression Initiate Sprouting Angiogenesis

Objective: VEGF (vascular endothelial growth factor) plays a critical role in physiological and pathological angiogenesis. Endothelial 3D podosomes (3DPs) are type of F-actin-rich membrane microdomain, predominantly found tip cells controlled by signaling during sprouting angiogenesis, such as occurs retinal vasculature development. The molecular mechanisms governing 3DP formation have not been completely elucidated. Approach Results: By using vitro cell models vivo mouse models, we study the TM (thrombomodulin) VEGF-induced 3DPs. Here, report that can induce expression via ROCK2 (Rho-associated coiled-coil kinase 2). Furthermore, catalyze phosphorylated activation ezrin to promote association cytoplasmic domain with F-actin 3DPs thereby We used transfected different mutants verify domains angiogenic activity. augments activity, response is dependent on interaction tail ezrin, integrity lectin-like TM. Thus, compared wild-type counterparts, mice lacking exhibit reduced neovascularization granulation tissues cutaneous wound healing less model oxygen-induced retinopathy. Conclusions: VEGF-ROCK2-ezrin-TM-F-actin axis promotes lipid raft membrane-associated complex configuration, 3DP, which mediating tube migration