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ROS enhance angiogenic properties via regulation of NRF2 in tumor endothelial cells
This item is licensed under:Creative Commons Attribution 3.0 Unported
| 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)
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Submitter: 樋田 京子
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