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

Hojo, Takayuki; Maishi, Nako; Towfik, Alam Mohammad; Akiyama, Kosuke; Ohga, Noritaka; Shindoh, Masanobu; Hida, Kyoko; Minowa, Kazuyuki; Fujisawa, Toshiaki

doi:10.18632/oncotarget.17567

Cited by 40 publications

(25 citation statements)

References 44 publications

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“…A low degree of oxidative stress is thought to promote proper EC function and maintain the quiescent phenotype of ECs. In contrast, deregulated ROS levels in ECs promote angiogenesis and may become toxic [32].…”

Section: Autophagy In Ecsmentioning

confidence: 99%

Autophagy in endothelial cells and tumor angiogenesis

et al. 2019

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In mammalian cells, autophagy is the major pathway for the degradation and recycling of obsolete and potentially noxious cytoplasmic materials, including proteins, lipids, and whole organelles, through the lysosomes. Autophagy maintains cellular and tissue homeostasis and provides a mechanism to adapt to extracellular cues and metabolic stressors. Emerging evidence unravels a critical function of autophagy in endothelial cells (ECs), the major components of the blood vasculature, which delivers nutrients and oxygen to the parenchymal tissue. EC-intrinsic autophagy modulates the response of ECs to various metabolic stressors and has a fundamental role in redox homeostasis and EC plasticity. In recent years moreover, genetic evidence suggests that autophagy regulates pathological angiogenesis, a hallmark of solid tumors. In the hypoxic, nutrient-deprived, and pro-angiogenic tumor microenvironment, heightened autophagy in the blood vessels is emerging as a critical mechanism enabling ECs to dynamically accommodate their higher bioenergetics demands to the extracellular environment and connect with other components of the tumor stroma through paracrine signaling. In this review, we provide an overview of the major cellular mechanisms regulated by autophagy in ECs and discuss their potential role in tumor angiogenesis, tumor growth, and response to anticancer therapy.

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Section: Autophagy In Ecsmentioning

confidence: 99%

Autophagy in endothelial cells and tumor angiogenesis

et al. 2019

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“…Many studies have shown that ROS can activate Nrf2. 27,28 Therefore, our data strongly suggest that the imbalance of Nrf2-dependent redox in cardiomyocytes activated by NOX4-generated ROS is an important cause of myocardial fibrosis.…”

Section: Discussionmentioning

confidence: 71%

Effects of lunar dust simulant on cardiac function and fibrosis in rats

et al. 2019

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“…The expression of Nrf2 is critical for cell survival and vitality during oxidative process in vivo and in vitro. Hojo et al () discovered that excessive ROS could inhibit the expression of Nrf2 to promote the formation of tumor endothelial cells. Nrf2‐deficient mice were reported with the trend to develop the severe hemolysis due to reduced antioxidant capacity (J. M. Lee, Chan, Kan, & Johnson, ).…”

Section: Discussionmentioning

confidence: 99%

Syndecan‐4 involves in the pathogenesis of rheumatoid arthritis by regulating the inflammatory response and apoptosis of fibroblast‐like synoviocytes

Cai

Jiang

et al. 2019

Journal Cellular Physiology

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Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, and the pathogenesis of RA is still unknown. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) are of significance in the pathogenesis of RA. In this study, three microarray profiles (GSE55457, GSE55584, and GSE55235) of human joint FLSs from 33 RA patients and 20 normal controls were extracted from the Gene Expression Omnibus Dataset and analyzed to investigate the underlying pathogenesis of RA. As analyzed by the differently expressed genes, gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein-protein interaction network analysis, syndecan-4 (SDC4), a receptor of multiple cytokines and chemokines, which played a key role in the regulation of inflammatory response, was found to be an essential regulator in RA. To further validate these results, the levels of SDC4, reactive oxygen species (ROS), nitric oxide (NO), inflammation, and apoptosis in RA-FLSs were examined. SDC4-silenced RA-FLSs were also used. The results demonstrated that SDC4 and the level of ROS, NO, and inflammation were highly expressed while the apoptosis was decreased in RA-FLSs compared with normal FLSs. SDC4 silencing significantly suppressed the levels of ROS, NO, and inflammation; elevated the expression of nuclear factor erythroid 2-related factor 2; and promoted the apoptosis of RA-FLSs. Collectively, our results demonstrated a new mechanism of SDC4 in initiating the inflammation and inhibiting the apoptosis of RA-FLSs and that a potential target for the diagnosis and treatment of RA in the clinic might be developed. K E Y W O R D Sapoptosis, fibroblast-like synoviocytes, inflammation, rheumatoid arthritis, syndecan-4

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

Cited by 40 publications

References 44 publications

Autophagy in endothelial cells and tumor angiogenesis

Autophagy in endothelial cells and tumor angiogenesis

Effects of lunar dust simulant on cardiac function and fibrosis in rats

Syndecan‐4 involves in the pathogenesis of rheumatoid arthritis by regulating the inflammatory response and apoptosis of fibroblast‐like synoviocytes

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