Ets-1 Is a Critical Transcriptional Regulator of Reactive Oxygen Species and p47
            <sup>
              <i>phox</i>
            </sup>
            Gene Expression in Response to Angiotensin II

Ni, Weihua; Zhan, Yumei; He, Hongqing; Maynard, Elizabeth; Balschi, James A.; Oettgen, Peter

doi:10.1161/circresaha.107.152439

Cited by 80 publications

(67 citation statements)

References 39 publications

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“…For these studies, and as we have done in previous studies, we took advantage of the availability of an ETS-1-dominant negative peptide to block the effects of ETS-1 and of a mutant inactive peptide that was used as control. 36 Our studies demonstrate that the administration of ETS-DN reduces the expression of NOS2, NOX2, NOX4, MCP-1, and E-selectin 3 weeks after the creation of AVF. These findings indicate that ETS-1 regulates the expression of several mediators involved in the formation of neointima in AVF, including chemoattractant molecules, adhesion molecules, and vascular sources of ROS and NO.…”

Section: Discussionsupporting

confidence: 50%

“…ETS-1 blockade did not significantly modify the expression of the NOX subunits p47phox and p67phox or the adhesion molecule VCAM, suggesting that ETS-1 regulates the expression of some but not all potential mediators of neointima formation in AVF. We previously demonstrated that ETS-1 directly regulates the expression of fibronectin 32 in rat mesangial cells, and studies by others have demonstrated that ETS-1 directly regulates the expression of MCP-1 14 and p47phox 36 in arterial vascular smooth muscle cells stimulated with angiotensin II. In our studies we could not demonstrate that ETS-1 regulates p47phox, which suggests the presence of tissue differences in the regulation of this NOX subunit by ETS-1.…”

Section: Discussionmentioning

confidence: 91%

“…31 Mice belonging to the different groups were euthanized 1 or 3 weeks after surgery. The ETS-DN and inactive ETS-MU peptides were synthesized (CPC Scientific, Inc., San Jose, CA) following the sequences described by Ni et al 36 …”

Section: Experimental Protocolmentioning

confidence: 99%

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The Transcription Factor E26 Transformation–Specific Sequence-1 Mediates Neointima Formation in Arteriovenous Fistula

Feng¹,

Chumley²,

Allon³

et al. 2014

Journal of the American Society of Nephrology

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Hemodialysis vascular access dysfunction contributes to increased morbidity and mortality in hemodialysis patients. Arteriovenous fistula (AVF) is the preferred type of vascular access for hemodialysis but has high rates of dysfunction, in part because of excessive neointima formation. The transcription factor E26 transformation-specific sequence-1 (ETS-1) is a mediator of proinflammatory responses in hypertension and endovascular injury. We examined the role of ETS-1 in the formation of neointima in AVF. Right carotid artery to internal jugular vein fistulas were created in C57BL/6 mice and assigned to treatment with an ETS-1-dominant negative peptide (ETS-DN), an inactive mutant peptide (ETS-MU), or vehicle (n=6 per group). After 7 and 21 days, AVFs or contralateral internal jugular veins were processed for PCR, immunofluorescence, immunohistochemistry, and morphometry. In AVFs, ETS-1 mRNA increased 2.5-fold at 7 days and 4-fold at 21 days. By immunofluorescence, we confirmed increased expression of ETS-1 predominantly in the neointima and overlying endothelium. Similarly, ETS-1 expression increased in human AVFs compared with normal veins. In mice, ETS-DN, but not ETS-MU, reduced neointima formation at days 7 and 21 and reduced the expression of nitric oxide synthase 2, NADPH oxidase (NOX) 2, NOX4, E-selectin, and monocyte chemotactic protein-1. Shear stress increased ETS-1 phosphorylation in human umbilical vein cells in a NOX-dependent manner, demonstrating a role for reactive oxygen species in ETS-1 activation. These results unveil the role of ETS-1 as a mediator of neointima formation in AVF and may result in the development of novel strategies for the treatment of AVF dysfunction.

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Section: Discussionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 91%

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The Transcription Factor E26 Transformation–Specific Sequence-1 Mediates Neointima Formation in Arteriovenous Fistula

Feng¹,

Chumley²,

Allon³

et al. 2014

Journal of the American Society of Nephrology

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“…Ets-1 is a key transcription factor that is known to support angiogenesis. Certain pro-angiogenic stimulus such as VEGF (30,31), angiotensin II (32,33), and fibroblast growth factor (FGF) (34) induce Ets-1 expression. In vitro scratch wound on the monolayer of confluent human endothelial cells up-regulated Ets-1 expression specifically in migrating edges, whereas it returned back to the basal level after wound closure completion (35).…”

Section: Hypoxia-induced Ets-1 Up-regulation and Angiogenic Response mentioning

confidence: 99%

miR-200b Targets Ets-1 and Is Down-regulated by Hypoxia to Induce Angiogenic Response of Endothelial Cells

Chan

Khanna

Roy

et al. 2011

Journal of Biological Chemistry

223

183

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Micro-RNAs (miRs)2 are small non-coding RNAs consisting of ϳ22 nucleotide base pairs. These small nucleic acids could regulate gene expression by binding to the 3Ј untranslated region (3Ј UTR) of mRNA, resulting in either translational repression or transcript degradation. Around 30% of the genes in the whole genome are subjected to regulation by miRs (1). Because of the short sequence requirement for binding the target 3Ј UTR, a single miR could interact with a wide range of target transcripts, which could substantially alter gene expression and dictate cell fate such as proliferation, apoptosis, and cell migration.Angiogenesis, the formation of vessels from the existing vascular structure, is a crucial biological response in wound healing, menstrual cycle, tumor aggression, and diabetic retinopathy. Endothelial sprouting, which requires extracellular matrix remodeling and endothelial cell migration, is the prerequisite process of angiogenic response. Such biological response relies on highly coordinated gene expression in a temporal and spatial manner. Increasing evidence revealed that miRs play a pivotal role in the angiogenic process. Our group and others reported that dicer, a ribonuclease III catalyzing miR maturation, is involved in the angiogenic process in human endothelial cells (2-4). Endothelial-specific dicer knockout mice exhibited an impaired angiogenic response (5). Certain miRs such as miR-126 and miR-296 have been shown to exert pro-angiogenic effects, whereas other reports indicated that miR-130a, -221, and -222 inhibited angiogenesis (6). Recently, the miR-200 family has been shown to arrest cell migration and modulate epithelial-mesenchymal transition in a wide range of epithelial cancer cells (7-12). We hypothesized that miR-200b, one member in miR-200 family, regulates endothelial cell migration and angiogenic responses. In this study, we present the first evidence demonstrating that miR200b is hypoxia-inducible and down-regulates v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets-1), a novel direct target of miR-200b, subsequently promoting angiogenic response of HMEC. EXPERIMENTAL PROCEDURESCells, Cell Culture, and Hypoxic Treatment-Human dermal microvascular endothelial cells (HMECs) were cultured in a humidified chamber (37°C, 20% O 2 and 5% CO 2 ) in MCDB-131 medium supplemented with 10% FBS, 10 mM Lglutamine, and 100 IU/ml of penicillin, 0.1 mg/ml of streptomycin (Invitrogen), as described previously (3). Primary adult human dermal microvascular endothelial cells were cultured at 37°C (20% O 2 and 5% CO 2 ) in EBM-2 medium (Lonza) supplemented with EGM-2MV single quotes (Lonza) as described by the manufacturer. HEK-293 cells were grown at standard cell culture conditions (37°C, 20% O 2 and 5% CO 2 ) with DMEM supplemented with 10% FBS and 100 IU/ml of penicillin, 0.1 mg/ml of streptomycin. For hypoxic treatment, cells were seeded on a 35-mm dish at 0.5 ϫ 10 6 cells/plate 1 * This work was supported, in whole or in part, by National Institutes of Health Grants GM077185 and GM069...

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“…Preliminary data showed that both RFK and Ets expression were also induced by treatment with cisplatin or H 2 O 2 (data not shown). It has been recently shown that the expression of Ets is a critical transcription factor of ROS stress (28) and that there is one Ets binding site in the promoter region of the RFK gene. These data suggest that stress-dependent activation of the Ets-related transcriptional factors might be involved in the regulation of RFK.…”

Section: Discussionmentioning

confidence: 99%

Involvement of riboflavin kinase expression in cellular sensitivity against cisplatin

et al. 2011

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Abstract. Flavin adenine dinucleotide (FAD) is an essential coenzyme for glutathione reductase (GR) which catalyzes the reduction of oxidized glutathione to regenerate the reduced form involved in protection against oxidative stress. Riboflavin kinase (RFK) also known as flavokinase is involved in the first step of bioactivation of riboflavin (RF) to form flavin mononucleotide (FMN) which can be subsequently converted to FAD in an ATP-dependent reaction catalyzed by FAD synthetase (FADS). We investigated the involvement of RFK in cisplatin resistance using human prostate cancer PC3 cells. RFK overexpression renders cells resistant not only to cisplatin but also to hydrogen peroxide (H 2 O 2 ) and diamide. Furthermore, knockdown of RFK expression induced apoptosis. We demonstrated that overexpression of RFK increased the levels of FAD, FMN and total glutathione and the expression of GR and glutathione S-transferase-π (GSTπ). RFK expression is up-regulated in cisplatin-resistant P/CDP6 cells in addition to FAD, total glutathione level, GR and GSTπ. Knockdown of RFK expression also sensitized both PC3 and P/CDP6 cells to cisplatin. Moreover, cellular levels of RFK expression correlate well with Gleason score, known as a good indicator of patient prognosis. The present study suggests that RFK expression is involved not only in cellular protection from oxidative stress but also in malignant progression of prostate cancer.

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Ets-1 Is a Critical Transcriptional Regulator of Reactive Oxygen Species and p47 ^phox Gene Expression in Response to Angiotensin II

Cited by 80 publications

References 39 publications

The Transcription Factor E26 Transformation–Specific Sequence-1 Mediates Neointima Formation in Arteriovenous Fistula

The Transcription Factor E26 Transformation–Specific Sequence-1 Mediates Neointima Formation in Arteriovenous Fistula

miR-200b Targets Ets-1 and Is Down-regulated by Hypoxia to Induce Angiogenic Response of Endothelial Cells

Involvement of riboflavin kinase expression in cellular sensitivity against cisplatin

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Ets-1 Is a Critical Transcriptional Regulator of Reactive Oxygen Species and p47 phox Gene Expression in Response to Angiotensin II

Cited by 80 publications

References 39 publications

The Transcription Factor E26 Transformation–Specific Sequence-1 Mediates Neointima Formation in Arteriovenous Fistula

The Transcription Factor E26 Transformation–Specific Sequence-1 Mediates Neointima Formation in Arteriovenous Fistula

miR-200b Targets Ets-1 and Is Down-regulated by Hypoxia to Induce Angiogenic Response of Endothelial Cells

Involvement of riboflavin kinase expression in cellular sensitivity against cisplatin

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Ets-1 Is a Critical Transcriptional Regulator of Reactive Oxygen Species and p47 ^phox Gene Expression in Response to Angiotensin II