| Literature DB >> 28350986 |
Hiroyuki Nakajima1, Kimiko Yamamoto2, Sobhika Agarwala3, Kenta Terai4, Hajime Fukui1, Shigetomo Fukuhara5, Koji Ando1, Takahiro Miyazaki1, Yasuhiro Yokota1, Etienne Schmelzer6, Heinz-Georg Belting6, Markus Affolter6, Virginie Lecaudey7, Naoki Mochizuki8.
Abstract
Endothelial cells (ECs) line the inside of blood vessels and respond to mechanical cues generated by blood flow. Mechanical stimuli regulate the localization of YAP by reorganizing the actin cytoskeleton. Here we demonstrate blood-flow-mediated regulation of endothelial YAP in vivo. We indirectly monitored transcriptional activity of Yap1 (zebrafish YAP) and its spatiotemporal localization in living zebrafish and found that Yap1 entered the nucleus and promoted transcription in response to blood flow. In cultured human ECs, laminar shear stress induced nuclear import of YAP and its transcriptional activity in a manner independent of Hippo signaling. We uncovered a molecular mechanism by which flow induced the nuclear translocation of YAP through the regulation of filamentous actin and angiomotin. Yap1 mutant zebrafish showed a defect in vascular stability, indicating an essential role for Yap1 in blood vessels. Our data imply that endothelial Yap1 functions in response to flow to maintain blood vessels.Entities:
Keywords: Hippo pathway; fluid shear stress; mechanotransduction; vascular remodeling
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Year: 2017 PMID： 28350986 DOI： 10.1016/j.devcel.2017.02.019
Source DB: PubMed Journal: Dev Cell ISSN： 1534-5807 Impact factor: 12.270