YAP/TAZ regulates sprouting angiogenesis and vascular barrier maturation

• DOI: 10.1172/jci93825
• Publication Date: 2017-08-13T22:00:23Z
• Authors: Jongshin Kim; Yoo Hyung Kim; Jaeryung Kim; Do Young Park; Hosung Bae; Da-Hye Lee; Kyun Hoo Kim; Seon Pyo Hong; Seung Pil Jang; Yoshiaki Kubota; Young-Guen Kwon; Dae-Sik Lim; Gou Young Koh
• Keywords: Sprouting angiogenesis; Adherens junction; Filopodia; Hippo signaling pathway

Angiogenesis is a multistep process that requires coordinated migration, proliferation, and junction formation of vascular endothelial cells (ECs) to form new vessel branches in response growth stimuli. Major intracellular signaling pathways regulate angiogenesis have been well elucidated, but key transcriptional regulators mediate these control EC behaviors are only beginning be understood. Here, we show YAP/TAZ, coactivator acts as an end effector Hippo signaling, critical for sprouting barrier maturation. In mice, endothelial-specific deletion Yap/Taz led blunted-end, aneurysm-like tip ECs with fewer dysmorphic filopodia at the front, hyper-pruned network, reduced disarranged distributions tight adherens proteins, disrupted integrity, subsequent hemorrhage growing retina brain vessels, pathological choroidal neovascularization. Mechanistically, YAP/TAZ activates actin cytoskeleton remodeling, important component assembly. Moreover, coordinates proliferation metabolic activity by upregulating MYC signaling. Overall, results plays multifaceted roles behaviors, assembly, metabolism maturation could potential therapeutic target treating neovascular diseases.