YAP/TAZ regulates sprouting angiogenesis and vascular barrier maturation Highly Cited Paper

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Title
YAP/TAZ regulates sprouting angiogenesis and vascular barrier maturation
Author(s)
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
Publication Date
2017-09
Journal
JOURNAL OF CLINICAL INVESTIGATION, v.127, no.9, pp.3447 - 3467
Publisher
AMER SOC CLINICAL INVESTIGATION INC
Abstract
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 to growth stimuli. Major intracellular signaling pathways that regulate angiogenesis have been well elucidated, but key transcriptional regulators that mediate these signaling pathways and control EC behaviors are only beginning to be understood. Here, we show that YAP/TAZ, a transcriptional coactivator that acts as an end effector of Hippo signaling, is critical for sprouting angiogenesis and vascular barrier formation and maturation. In mice, endothelial-specific deletion of Yap/Taz led to blunted-end, aneurysm-like tip ECs with fewer and dysmorphic filopodia at the vascular front, a hyper-pruned vascular network, reduced and disarranged distributions of tight and adherens junction proteins, disrupted barrier integrity, subsequent hemorrhage in growing retina and brain vessels, and reduced pathological choroidal neovascularization. Mechanistically, YAP/TAZ activates actin cytoskeleton remodeling, an important component of filopodia formation and junction assembly. Moreover, YAP/TAZ coordinates EC proliferation and metabolic activity by upregulating MYC signaling. Overall, these results show that YAP/TAZ plays multifaceted roles for EC behaviors, proliferation, junction assembly, and metabolism in sprouting angiogenesis and barrier formation and maturation and could be a potential therapeutic target for treating neovascular diseases.
URI
https://pr.ibs.re.kr/handle/8788114/4089
ISSN
0021-9738
Appears in Collections:
Center for Cardiovascular Research(혈관 연구단) > Journal Papers (저널논문)
Files in This Item:
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