ESE-1 Is a Novel Transcriptional Mediator of Angiopoietin-1 Expression in the Setting of Inflammation

Brown, Courtney; Gaspar, John; Pettit, Allison R.; Lee, Rebecca; Gu, Xuesong; Wang, Hong; Manning, Cathy; Voland, Carole; Goldring, Steven R.; Goldring, Mary B.; Libermann, Towia A.; Gravallese, Ellen M.; Oettgen, Peter

doi:10.1074/jbc.m308593200

Cited by 57 publications

(60 citation statements)

References 49 publications

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“…With respect to an important role in angiogenesis, we selected VEGF receptors and angiopoietins. VEGFR2, or Flk-1 and angiopoietin-2 have been described as ETS-1 target genes (Elvert et al, 2003;Hasegawa et al, 2004), whereas angiopoietin-1 is stimulated by ESE-1 from the group of ETS transcription factors, but not by ETS-1 (Brown et al, 2004). In agreement with this, we detected a downregulation of angiopoietin-2 and VEGFR2, but not of angiopoietin-1 in WT1-silenced endothelial cells.…”

Section: Wt1 Activates Ets-1 In Endothelial Cellssupporting

confidence: 89%

“…In transient transfection experiments, deletion of the identified binding site abolished activation of the ETS-1 promoter by the WT1(ÀKTS) splice variant (Figure 7d). Since angiopoietin-2 (Hasegawa et al, 2004) and the vascular endothelial growth factor receptor 2 (VEGFR2) (Elvert et al, 2003), but not angiopoietin-1 (Brown et al, 2004), have been described as a transcriptional targets of ETS-1, we analysed the expression of angiopoietin-1 and -2, and VEGFR2 in WT1-silenced cells, which show reduced levels of ETS-1 protein. Indeed, angiopoietin-2 and VEGFR2 expression levels were lower in WT1-silenced cells compared to controls whereas angiopoietin-1 was unchanged (Figure 7e).…”

Section: The Ets-1 Transcription Factor Is Regulated By Wt1mentioning

confidence: 99%

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The Wilms' tumour suppressor WT1 is involved in endothelial cell proliferation and migration: expression in tumour vessels in vivo

Wagner

Schedl

et al. 2008

Oncogene

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Vascularization is an important step in tumour growth. Although a variety of molecules, for example, VEGF, ETS-1 or nestin have been implicated in tumour angiogenesis, the molecular mechanisms of vessel formation are not fully characterized. We showed that the Wilms' tumour suppressor WT1 activates nestin during development. Here we tested whether WT1 might also be involved in tumour angiogenesis. Endothelial WT1 expression was detected in 95% of 113 tumours of different origin. To analyse the function of WT1 in endothelial cells, we used an RNAi approach in vitro and showed that inhibition of WT1 reduces cell proliferation, migration and endothelial tube formation. On a molecular level, WT1 silencing diminished expression of the ETS-1 transcription factor. WT1 and ETS-1 shared an overlapping expression in tumour endothelia. The ETS-1 promoter was stimulated approximately 10-fold by transient co-transfection of a WT1 expression construct and WT1 bound to the ETS-1 promoter in chromatin immunoprecipitation and electrophoretic mobility shift assays. Deletion of the identified WT1-binding site abolished stimulation of the ETS-1 promoter by WT1. These findings suggest that transcriptional activation of ETS-1 by the Wilms' tumour suppressor WT1 is a crucial step in tumour vascularization via regulation of endothelial cell proliferation and migration.

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Section: Wt1 Activates Ets-1 In Endothelial Cellssupporting

confidence: 89%

Section: The Ets-1 Transcription Factor Is Regulated By Wt1mentioning

confidence: 99%

The Wilms' tumour suppressor WT1 is involved in endothelial cell proliferation and migration: expression in tumour vessels in vivo

Wagner

Schedl

et al. 2008

Oncogene

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“…Although the expression of ESEs is normally confined to epithelial cells, cytokineregulated ESE expression exists in other cell types. For example, in response to inflammatory cytokines, ESE-1 is expressed in monocytes [23], chondrocytes and fibroblasts [24,25]. We report here that the expression of ESE-1 and ESE-3 in airway epithelial cells can be dramatically enhanced by inflammatory cytokines.…”

Section: Discussionmentioning

confidence: 72%

“…To examine whether ESE-1 and ESE-3 expression in epithelial cells can be induced by IL-1β and/or TNF-α as in non-epithelial cells [23][24][25][26], we stimulated cultured human bronchial epithelial cells (BEAS-2B) with IL-1β and/or TNF-α. Using semi-quantitative RT-PCR (data not shown), we detected increased ESE-1 and ESE-3 but not ESE-2 mRNA expression after cytokine induction.…”

Section: Ese-1 and Ese-3 Are Upregulated In Bronchial Epithelial Cellmentioning

confidence: 99%

“…The expression of ESE-1 can be induced by inflammatory cytokines (IL-1β and TNF-α) in cultured non-epithelial cells, such as vascular smooth muscle cells, endothelial cells, monocytes [23] and fibroblasts [24,25]. ESE-3 mRNA expression is induced in bronchial smooth muscle cells and fibroblasts and is constitutively expressed in human bronchial epithelial cells [26].…”

Section: Introductionmentioning

confidence: 99%

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Regulation of epithelium-specific Ets-like factors ESE-1 and ESE-3 in airway epithelial cells: potential roles in airway inflammation

Duan

Cao

et al. 2008

Cell Res

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Airway inflammation is the hallmark of many respiratory disorders, such as asthma and cystic fibrosis. Changes in airway gene expression triggered by inflammation play a key role in the pathogenesis of these diseases. Genetic linkage studies suggest that ESE-2 and ESE-3, which encode epithelium-specific Ets-domain-containing transcription factors, are candidate asthma susceptibility genes. We report here that the expression of another member of the Ets family transcription factors ESE-1, as well as ESE-3, is upregulated by the inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in bronchial epithelial cell lines. Treatment of these cells with IL-1β and TNF-α resulted in a dramatic increase in mRNA expression for both ESE-1 and ESE-3. We demonstrate that the induced expression is mediated by activation of the transcription factor NF-κB. We have characterized the ESE-1 and ESE-3 promoters and have identified the NF-κB binding sequences that are required for the cytokine-induced expression. In addition, we also demonstrate that ESE-1 upregulates ESE-3 expression and downregulates its own induction by cytokines. Finally, we have shown that in Elf3 (homologous to human ESE-1) knockout mice, the expression of the inflammatory cytokine interleukin-6 (IL-6) is downregulated. Our findings suggest that ESE-1 and ESE-3 play an important role in airway inflammation.

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ESE‐1 is a potent repressor of type II collagen gene (COL2A1) transcription in human chondrocytes

Peng

Tan

Osaki

et al. 2007

Journal Cellular Physiology

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The epithelium-specific ETS (ESE)-1 transcription factor is induced in chondrocytes by interleukin-1β (IL-1β). We reported previously that early activation of EGR-1 by IL-1β results in suppression of the proximal COL2A1 promoter activity by displacement of Sp1 from GC boxes. Here we report that ESE-1 is a potent transcriptional suppressor of COL2A1 promoter activity in chondrocytes and accounts for the sustained, NF-κB-dependent inhibition by . Of the ETS factors tested, this response was specific to ESE-1, since ESE-3, which was also induced by IL-1β, suppressed COL2A1 promoter activity only weakly. In contrast, overexpression of ETS-1 increased COL2A1 promoter activity and blocked the inhibition by IL-1β. These responses to ESE-1 and ETS-1 were confirmed using siRNA-ESE1 and siRNA-ETS1. In transient cotransfections, the inhibitory responses to ESE-1 and IL-1β colocalized in the -577/-132 bp promoter region, ESE-1 bound specifically to tandem ETS sites at 403/ 381 bp, and IL-1-induced binding of ESE-1 to the COL2A1 promoter was confirmed in vivo by ChIP. Our results indicate that ESE-1 serves a potent repressor function by interacting with at least two sites in the COL2A1 promoter. However, the endogenous response may depend upon the balance of other ETS factors such as ETS-1, and other IL-1-induced factors, including EGR-1 at any given time. Intracellular ESE-1 staining in chondrocytes in cartilage from patients with osteoarthritis (OA), but not in normal cartilage, further suggests a fundamental role for ESE-1 in cartilage degeneration and suppression of repair.The chondrocyte is a specialized mesenchymal cell that synthesizes matrix proteins responsible for the tensile strength and resistance to mechanical loading of the articular cartilage (Poole, 2005). In adult articular cartilage, the chondrocytes maintain a low turnover rate of replacement of cartilage matrix proteins. Collagen turnover has been estimated to occur with a half-life of greater than 100 years, whereas the glycosaminoglycan constituents on the aggrecan core protein are more readily replaced and the half-life of aggrecan subfractions is in the range of 3-24 years. Nevertheless, chondrocytes in vivo respond to NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript structural changes in the surrounding cartilage matrix as occurs during the initial stages of osteoarthritis (OA) when increased cell proliferation and synthesis of matrix proteins, proteinases, and cytokines are observed. The early changes in synthetic activity are viewed as an attempt to regenerate the matrix with cartilage-specific components, including types II, IX, and XI collagens and aggrecan, and the presence of collagens not normally found in adult articular cartilage is evidence of phenotypic modulation (Sandell and Aigner, 2001). Genomic and proteomic analyses of global gene expression cartilage have confirmed the increased levels of type II collagen (COL2A1) mRNA and protein in OA cartilage (Bau et al., 2002;Hermansson et al., 2004), possibly ...

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ESE-1 Is a Novel Transcriptional Mediator of Angiopoietin-1 Expression in the Setting of Inflammation

Cited by 57 publications

References 49 publications

The Wilms' tumour suppressor WT1 is involved in endothelial cell proliferation and migration: expression in tumour vessels in vivo

The Wilms' tumour suppressor WT1 is involved in endothelial cell proliferation and migration: expression in tumour vessels in vivo

Regulation of epithelium-specific Ets-like factors ESE-1 and ESE-3 in airway epithelial cells: potential roles in airway inflammation

ESE‐1 is a potent repressor of type II collagen gene (COL2A1) transcription in human chondrocytes

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