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ROS enhance angiogenic properties via regulation of NRF2 in tumor endothelial cells

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Title: ROS enhance angiogenic properties via regulation of NRF2 in tumor endothelial cells
Authors: Hojo, Takayuki Browse this author
Maishi, Nako Browse this author →KAKEN DB
Towfik, Alam Mohammad Browse this author
Akiyama, Kosuke Browse this author →KAKEN DB
Ohga, Noritaka Browse this author →KAKEN DB
Shindoh, Masanobu Browse this author →KAKEN DB
Hida, Yasuhiro Browse this author →KAKEN DB
Minowa, Kazuyuki Browse this author
Fujisawa, Toshiaki Browse this author →KAKEN DB
Hida, Kyoko Browse this author →KAKEN DB
Keywords: tumor angiogenesis
tumor endothelial cells
reactive oxygen species
biglycan
nuclear factor erythroid 2-related factor 2
Issue Date: 11-Jul-2017
Publisher: Impact Journals
Journal Title: Oncotarget
Volume: 8
Issue: 28
Start Page: 45484
End Page: 45495
Publisher DOI: 10.18632/oncotarget.17567
Abstract: Reactive oxygen species (ROS) are unstable molecules that activate oxidative stress. Because of the insufficient blood flow in tumors, the tumor microenvironment is often exposed to hypoxic condition and nutrient deprivation, which induces ROS accumulation. We isolated tumor endothelial cells (TECs) and found that they have various abnormalities, although the underlying mechanisms are not fully understood. Here we showed that ROS were accumulated in tumor blood vessels and ROS enhanced TEC migration with upregulation of several angiogenesis related gene expressions. It was also demonstrated that these genes were upregulated by regulation of Nuclear factor erythroid 2-related factor 2 (NRF2). Among these genes, we focused on Biglycan, a small leucine-rich proteoglycan. Inhibition of Toll-like receptors 2 and 4, known BIGLYCAN (BGN) receptors, cancelled the TEC motility stimulated by ROS. ROS inhibited NRF2 expression in TECs but not in NECs, and NRF2 inhibited phosphorylation of SMAD2/3, which activates transcription of BGN. These results indicated that ROS-induced BGN caused the pro-angiogenic phenotype in TECs via NRF2 dysregulation.
Rights: http://creativecommons.org/licenses/by/3.0/
Type: article
URI: http://hdl.handle.net/2115/67123
Appears in Collections:遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 樋田 京子

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