YAP/TAZ regulates sprouting angiogenesis and vascular barrier maturation.

Details

Serval ID
serval:BIB_7BBAE7A68865
Type
Article: article from journal or magazin.
Collection
Publications
Title
YAP/TAZ regulates sprouting angiogenesis and vascular barrier maturation.
Journal
The Journal of clinical investigation
Author(s)
Kim J., Kim Y.H., Kim J., Park D.Y., Bae H., Lee D.H., Kim K.H., Hong S.P., Jang S.P., Kubota Y., Kwon Y.G., Lim D.S., Koh G.Y.
ISSN
1558-8238 (Electronic)
ISSN-L
0021-9738
Publication state
Published
Issued date
01/09/2017
Peer-reviewed
Oui
Volume
127
Number
9
Pages
3441-3461
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
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.
Keywords
Actin Cytoskeleton/metabolism, Adaptor Proteins, Signal Transducing/metabolism, Animals, Cell Proliferation, Electroretinography, Extracellular Matrix/metabolism, Female, Gene Deletion, Hippo Signaling Pathway, Human Umbilical Vein Endothelial Cells, Humans, Intracellular Signaling Peptides and Proteins/metabolism, Intracranial Hemorrhages/metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neovascularization, Pathologic, Permeability, Phenotype, Protein Serine-Threonine Kinases/metabolism, Signal Transduction, Trans-Activators, Transcription Factors, Transcriptional Coactivator with PDZ-Binding Motif Proteins
Pubmed
Web of science
Open Access
Yes
Create date
10/03/2022 9:53
Last modification date
11/03/2022 7:33
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