2007; stem cells, and it has been suggested that these . a: H & E demonstrates a vascular lumen. ETS factors regulate specific target genes through combinatorial promoter motifs and interaction with other transcription factors. The query dataset were the 1138 genes identified as being up-regulated following a 48-h Erg inhibition in HUVEC (16), which were then compared against all the studies in the C2 curated gene sets. This article contains supplemental Table S1 and Figs. This showed that Erg binds to the promoter of cIAP2. . 3A, lane 4, arrowhead) and a decrease in the intensity of a complex (Fig. In this study we investigate the mechanisms used by Erg to repress inflammatory gene expression in quiescent EC, focusing on ICAM-1 as a model gene. The oligonucleotide containing EBS 118 formed a number of complexes with nuclear proteins from resting HUVEC (Fig. In agreement with previous data (12), inhibition of Erg expression by Genebloc antisense significantly increased wild type (WT) ICAM-1 promoter activity by 1.66-fold, compared with control (Fig. A method for rapid flow-cytometric isolation of endothelial nuclei and RNA from archived frozen brain tissue. FZD4 as a mediator of ERG oncogene-induced WNT signaling and epithelial-to-mesenchymal transition in human prostate cancer cells. Embryonic Pericytes Promote Microglial Homeostasis and Their Effects on Neural Progenitors in the Developing Cerebral Cortex. Endothelial cells form the barrier between vessels and tissue and control the flow of substances and fluid into and out of a tissue. ERG silence in HUVECs promotes the secretion of endothelin-1, which in turn activates cardiac fibroblasts in a paracrine manner. D and E, ChIP was carried out using an anti-Erg or control IgG antibody on sheared chromatin from confluent resting HUVEC (D) or HUVEC treated with Erg or control siRNA (E). The ICAM-1 promoter EBS mutants 96, 153, 358, 834, and 907 also showed significantly increased promoter activity after Erg inhibition. Previously, using an ICAM-1 promoter luciferase construct containing the first 1.3 kb upstream of the ICAM-1 transcription start site, we have shown that Erg represses ICAM-1 promoter activity in resting EC (12). We suggest that in quiescent EC, Erg acts as a gatekeeper, to inhibit the activity of low constitutive levels of nuclear NF-B p65 and protect the endothelium from the up-regulation of proinflammatory genes, thus maintaining quiescence. VAT will be added later in the checkout.Tax calculation will be finalised during checkout. A number of these EBS have been shown to play a role in ICAM-1 expression, including two AP1-EBS repeats involved in ICAM-1 induction after H2O2 stimulation (24), and two EBS that are involved in ICAM-1 expression in non-endothelial cells (2527). The first 1.3 kb upstream of the ICAM-1 transcription start site are required for ICAM-1 basal expression and regulation by inflammatory stimuli (23). SECTIONS. A.V.S. Deletion of ERG disrupts regulation of coagulation, leading to a. To identify which EBS are involved in Erg-mediated repression, we generated ICAM-1 promoter constructs with mutations within single EBS, or two EBS together, if they had previously been shown to have a cooperative role (24, 25). In combination with the current therapy, SSA had potential to improve treatment effectiveness and to prevent cancer recurrence. Mutations within more than one EBS were carried out sequentially. The ETS transcription factor family is implicated in vascular development and angiogenesis (reviewed in. This review highlights the adaptability of endothelial cells to support the function of each organ, while maintaining their endothelial cell fate. There are very few reports of primary venous hemangiomas in the literature. -catenin protein expression was restored in ERG-deficient EC in the presence of the proteosomal degradation inhibitor MG132 (. Analysis of the IL-8 promoter showed that the EBS identified as the binding site of Erg is located within the functional NF-B binding site, similarly to what was observed for ICAM-1 and cIAP2 (supplemental Fig. The ETS transcription factor ERG drives expression of VE-cadherinand controls junctional integrity. Accessibility S3). The normalized enrichment score (NES) reflects the degree to which a gene set is overrepresented at the top or bottom of a ranked list, normalized for differences in gene set size and in correlations between gene sets and the expression dataset (D, panel i) mRNA from HUVEC treated with Erg or control siRNA was analyzed by quantitative RT-PCR with primers specific for cIAP2 and normalized to GAPDH, expressed as relative to control siRNA-treated cells (n = 3), *, p < 0.05. Combined genomic and antisense analysis reveals that the transcription factor Erg is implicated in endothelial cell differentiation. To investigate whether the same applies to the other target genes investigated here, we tested whether Erg inhibits binding of NF-B p65 to the IL-8 and cIAP2 promoters. cIAP-2 was identified in all three studies used for the GSEA comparisons, whereas IL-8 was identified in the GSEA comparison with the study on TNF--treated EC (18) and was previously shown to be repressed by Erg (13). Gene Regulatory Network of ETS Domain Transcription Factors in Different Stages of Glioma. FEV expression is restricted to prostate and small intestine tissue (47) and Dami megakaryocytic cells (27). 3A, solid arrow), indicating that Erg binds to the EBS 118 site. pdf files, http://creativecommons.org/licenses/by/3.0/, Redistribute or republish the final article, Reuse portions or extracts from the article in other works. Cooperation of liver cells in health and disease. VEGF has been shown to induce the formation of unstable and highly permeable vessels invivo (. In this study, we identify a transcriptional program regulated by ERG that controls vascular stability and growth through the Wnt/-catenin pathway, in both a physiological and pathological context. PMC HUVEC were seeded onto 1% gelatin-coated plates and grown in EGM-2 medium (Lonza, Wokingham, United Kingdom). 15 a major regulator of adherent junctions is vascular endothelial (ve)-cadherin, a ca 2+ -dependent cell-surface adhesion molecule that forms homophilic interactions and is required for the integrity ISSN 2731-0590 (online). Hyperglycemia increases the risk of vascular complications such as diabetic retinopathy, diabetic nephropathy, peripheral vascular disease and cerebro/cardiovascular diseases. This site needs JavaScript to work properly. Immunoprecipitated DNA was then used as template for quantitative PCR using primers specific for the ICAM-1 promoter, cIAP2 promoter, IL-8 promoter, and the negative control gene GAPDH. D, panel ii, ChIP was carried out on sheared chromatin from confluent resting HUVEC, using an anti-Erg or control IgG antibody. In this study we identify a novel mechanism that controls endothelial quiescence through inhibition of NF-B activity. Taming of the wild vessel: promoting vessel stabilization for safe therapeutic angiogenesis. We thank M. Pitulescu (Max Planck Institute for Molecular Biomedicine, Mnster, Germany) for advice; H. Clevers (Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, Netherlands) for providing the TOPFLASH TCF reporter and control FOPFLASH plasmids; F.W. A recent paper has described a role for ETS factors (including ERG) in arterial specification and reported increased ERG expression in arterial-derived EC invitro (. Immunoprecipitated DNA was analyzed by qPCR for primers covering the NF-B site and EBS in cIAP2 (D, panel iii), or IL-8 (panel iv) (see supplemental Fig. The transcription factor Erg is essential for definitive hematopoiesis and the function of adult hematopoietic stem cells. Results are expressed as fold-change compared with IgG normalized to input and negative control region. 2010 Aug;113(2):218-24. doi: 10.3171/2009.10.JNS08631. L.O.A. Components of the protein-DNA complexes were investigated by the addition of anti-Erg (sc-353, Santa Cruz), anti-NF-B p65 (ab7970, AbCam), or IgG (PP64, Millipore) control antibodies. A., Scherer D. C., McKinsey T. A., Hall S. M., Qi X., Lee W. Y., Ballard D. W. (1995), Coupling of a signal response domain in IB to multiple pathways for NF-B activation, Transcriptional regulation of the intercellular adhesion molecule-1 gene by inflammatory cytokines in human endothelial cells. will also be available for a limited time. ENCODE ChIP-seq data profiles for H3K4me1, H3K27Ac, and RNA polymerase II indicate open chromatin and active transcription. There is growing evidence on the importance of transcription factor Erg in maintaining EC homeostasis. Dapper 1 antagonizes Wnt signaling by promoting dishevelled degradation. These markers and other endothelial markers are also discussed in Chapter 13. Briefly, pGL4 ICAM-1 1.3 plasmid was amplified using a primer designed to mutate a specific EBS from GGAA to CCAA or the NF-B site from TTGGAAATTCC to TTCTAGATTAG. (2021). Dynamic regulation of canonical TGFbeta signalling by endothelial transcription factor ERG protects from liver fibrogenesis. However, loss of the major complex after addition of NF-B p65 antibody suggests that, at least in vitro, nuclear NF-B p65 is able to bind to the EBS 181 oligonucleotide in resting HUVEC as well as in activated HUVEC. Endothelial cell (EC) plasticity in pathological settings has recently been recognized as a driver of disease progression. Dhaun N, Webb DJ. S1S3. In the absence of inflammatory stimuli, BCL6 recruited HDAC3 to promoters of NF-B target genes and repressed their transcription. Efficient direct reprogramming of mature amniotic cells into endothelial cells by ETS factors and TGF suppression. Common gene hits and accession numbers from GSEA analysis. S3) and a negative control GAPDH promoter region. Collectively, endothelial ERG alleviates cardiac fibrosis via blocking ET-1-dependent paracrine mechanism and it functions as a candidate for treating cardiac fibrosis. B.G. 3A, lane 7), confirming that Erg specifically interacts with the oligonucleotide containing EBS 118. This study aims at investigating the potential role and molecular basis of ERG in fibrotic remodeling within the adult heart. b: ERG, Figure 5.. HB. E ndothelial cells (EC) have many functions and play a central role in the control of coagulation, thrombolysis, vascular tone, permeability, inflammation, tissue repair, and angiogenesis. The recent years have witnessed an increased activity in biocompatibility research aimed at limiting biomaterial-induced blood coagulation. Clipboard, Search History, and several other advanced features are temporarily unavailable. ERG is a member of the ETS transcription factor family that is highly enriched in endothelial cells (ECs). Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis. We evaluated 57 CNS tumors, including glioblastomas (GBMs) and hemangioblastomas (HBs), as well as two arteriovenous malformations and four samples of normal brain tissue with immunohistochemistry using a specific ERG rabbit monoclonal antibody. More recently, ETV2 has been reported to transdifferentiate skeletal muscle into functional ECs in zebrafish . 1B), indicating that repression of ICAM-1 expression is not a shared property of constitutive ETS factors. 1C). 2014, Received in revised form: Loss of endothelial CFTR drives barrier failure and edema formation in lung infection and can be targeted by CFTR potentiation. Scale bar, 20m. https://doi.org/10.1038/s44161-022-00128-3, Cooperative ETS transcription factors enforce adult endothelial cell fate and cardiovascular homeostasis. Published by Elsevier Inc. We use cookies to help provide and enhance our service and tailor content. Because Erg also binds to this region, we investigated whether the presence of Erg inhibits the binding of NF-B p65 to DNA, by performing ChIP for NF-B p65 on HUVEC treated with Erg siRNA. Bookshelf 2014, Received: These results identify a role for Erg as a gatekeeper controlling vascular inflammation, thus providing an important barrier to protect against inappropriate endothelial activation. ERG knockdown causes spontaneously cardiac fibrosis and dysfunction. Thus, the ETS and GATA factors . 2019 Aug 20;140(8):665-680. doi: 10.1161/CIRCULATIONAHA.119.039767. Showing cell type specific RNA data of ERG (erg-3, p55). An official website of the United States government. sharing sensitive information, make sure youre on a federal (E) (Top) Representative whole mount images of E10.5. Alwahsh SM, Qutachi O, Starkey Lewis PJ, Bond A, Noble J, Burgoyne P, Morton N, Carter R, Mann J, Ferreira-Gonzalez S, Alvarez-Paino M, Forbes SJ, Shakesheff KM, Forbes S. Am J Transplant. ESCs have the characteristic properties of a stem cell: self-renewal and differentiation. pGL4 ICAM-1 1.3 was mutated in either single or double EBS or in the NF-B binding site. Cardiovas. Birdsey, G. M. et al. There were two labeled dextran molecules of different molecular weights, 210. June 13, CAS PMC legacy view Smad-dependent and Smad-independent pathways in TGF-beta family signalling. The more common types include capillary, cavernous, combined, and lobular capillary types. He was discharged from our hospital on postoperative day 6. Cancer. government site. (H) mRNA expression of Erg, -catenin, and its target genes Cyclin D1, Axin-2, and TCF-1 in primary, (I) qPCR analysis of total brain mRNA from control and, (J) GSEA shows enrichment and significant correlation (normalized enrichment score, 2.46; p< 0.001) between genes downregulated in -catenin siRNA-treated HPAEC (green curve) (. Mod Pathol. Epub 2010 May 24. B, Erg or control Genebloc-transfected HUVEC were treated with BAY-11-7085 or dimethyl sulfoxide (DMSO) control. HUVEC (1 105 cells/well) were seeded onto 1% gelatin-coated 6-well plates in supplemented M199 media. Of the top 9 studies with the most significant overlaps in regulated genes, two involved the response to treatment with the NF-B activating cytokine TNF-. We have previously investigated the genome-wide targets of Erg by transcription profiling of HUVEC treated with Erg Genebloc (16), and found that Erg represses a number of genes involved in inflammatory processes. Federal government websites often end in .gov or .mil. In the meantime, to ensure continued support, we are displaying the site without styles (D) Vascular density of isolectin B4 stained branches in the central plexus, scale bar, 50m; quantification (n= 6). Endothelial Cells Share Endothelial Cells Endothelial cells form the tunica intimathe thin layer of cells that line the interior surface of blood vessels. 3B, lanes 2 and 3). Erg represses ICAM-1 and binds to the ICAM-1 promoter region 4 in resting EC. and transmitted securely. Dev. Endothelial-to-mesenchymal transition (EndMT) is a phenomenon in which endothelial cells lose their characteristics and acquire mesenchymal-like properties. Hypoxia-ischemia induces the expression of hypoxia inducible factor-1 and its target genes such as vascular endothelial growth factor (VEGF) and nitric oxide synthase (NOS). Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. GSEA correlation of microarray data from Erg GeneBloc-treated HUVEC from the following published studies: TNF--treated pancreatic cancer cells (17), TNF--treated endothelial cells (18), NF-B p65 ChIP seq data (19), was performed using Gene Set Enrichment Analysis version 2.0 software using 1000 data permutations. 8600 Rockville Pike Endothelial ERG alleviates cardiac fibrosis via blocking endothelin-1 . Dynamic Phosphorylation of CENP-A at Ser68 Orchestrates Its Cell-Cycle-Dependent Deposition at Centromeres, Reverse Genetic Screening Reveals Poor Correlation between Morpholino-Induced and Mutant Phenotypes in Zebrafish, Endothelial ERG Is Required for Vascular Development, Angiogenesis, and Tumor Growth, ERG Is Required for Vascular Development, Physiological Postnatal Angiogenesis, and Pathological Tumor Angiogenesis, ERG Controls Vascular Stability and Pericyte Coverage, ERG Controls -Catenin Stability and Signaling through VE-Cadherin- and Wnt-Dependent Mechanisms, Endothelial Canonical Wnt Signaling and -Catenin Stability Are Regulated by ERG, ERG Controls -Catenin Stability through VE-Cadherin- and Wnt-Dependent Mechanisms, Expression of the Wnt Receptor Frizzled-4 Is Regulated byERG, Baylor College of Medicine Human Genome Sequencing Center, Washington University Genome Sequencing Center, Childrens Hospital Oakland Research Institute, ERG Controls Angiogenesis through Wnt Signaling, ERG Regulates Angiogenesis through Wnt/-Catenin Signaling, ERG Overexpression Stabilizes VEGF-Induced Blood Vessels and Promotes Angiogenesis InVivo, Isolation of Mouse Lung Endothelial Cells, Plasmid Transfections and Reporter Assays, eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI0MTE4MjEwN2VhMzAwMjI5Y2M1YTE0ZWY1ZDllNjA4OCIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjcwODIyNzE3fQ.n2t_EEIadOWDuBvYBM3qxbgnXUkqeUfJTf3R687qKZj_pnMqh3eIgs7tPeGSFW6wtKoPQsvfeQ2e5TaMM76aisnz580wH5QVG1dLFDmHCQpgnnDOct2_VHnSBX1CGX83q7xhXMGqUOUE-HNIfQxZ53P5GwfcnHh1lLJU74cT2FkyUg4J_mvbMyU9e2FhBmwbjsBfMQeAEIM0gKLuvF4lAhAd_IXnZlTR5ly4rlairqiIeoKF1qr6Q53jhqOvogcfAuJtwEenI0cy2VsXzNimB5zlXFGUZGkjHhhrf0_KiHdfZfw9C0ffYD0fg93UcxK4QXJzlX7g01j7zDxB91xtIw, eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI4ZjMzNWYwNjIyYjJmYmIzZmM0Y2M4ZGYwYzY5MzJmNCIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjcwODIyNzE3fQ.idar2V0x9cfoVI0p0kPMyjqj1i5F1H25HkaKd9fNUWIKAtgAtdUoD6q69na4nkTzLP-H2cJzVfx2bpwJOyx-S1IpEqKf0-YyNA0Nea9nSSHrbqGDpCi6GHWiUSM-V27KBzit9SsbsWal6a1aQMSbDQL1S_Y9POeP40CfrC_s4Pe6PAz-Gagozm5_MCh4FenMF6DVpiL0Ts3Vvz85NVmt0how8309XLFsJL_IrMuonIQjU6L71zYGkwTTdoU4D1JNyfLkSAxnoKAAPNkfZM61-fW0sLo7omTLvNNhAJQS7kv7ofGuPMeCa6yNbR7Q6Qa4ENhb7HQuQTRdq5xZKyhFew, https://doi.org/10.1016/j.devcel.2014.11.016, The Endothelial Transcription Factor ERG Promotes Vascular Stability and Growth through Wnt/-Catenin Signaling, View Large Provided by the Springer Nature SharedIt content-sharing initiative, Nature Cardiovascular Research (Nat Cardiovasc Res) 2C). (D and E) (D) Western blot and (E) qPCR analysis of -catenin expression in control (siCtrl) and ERG-deficient (siERG) HUVEC (n= 4). and S.T.K. This suggests that Erg is required to protect EC against a low level of inflammatory stimuli that may otherwise cause chronic activation and inflammation. Zhang, X., Hu, C., Yuan, Y.-P., Song, P., Kong, C.-Y., Wu, H.-M., Tang, Q.-Z. Background: In quiescent endothelial cells, the transcription factor Erg regulates cell homeostasis by repressing expression of proinflammatory genes. *, p < 0.05; **, p < 0.01. The https:// ensures that you are connecting to the 1A). This showed a decrease in the amount of Erg bound to R4 after Erg inhibition, compared with control siRNA treatment (Fig. C and D, ChIP was carried out on sheared chromatin from confluent resting HUVEC TNF (10 ng/ml for 30 min) (C), or HUVEC treated with Erg or control siRNA (D) using an anti-NF-B p65 or control IgG antibody. The .gov means its official. The cells can This subclass of tumour cells shows low AR expres- then remain dormant, interacting with native cells in sion and concomitant reduced PSA expression, which the niche, before proliferating to form a new tumour, frequently occurs in combination with loss of both which in turn has the . ERG can serve as a reliable marker of immature myeloid cells in cases of extramedullary hematopoiesis, bone marrow trephine biopsies and in adrenal myelolipomas ( Am J Surg Pathol 2011;35:432, Hum Pathol 2022;124:1 ) Reliably identifies the presence of ERG fusions in Ewing sarcomas ( Mod Pathol 2012;25:1378, Genes Chromosomes Cancer 2016;55:340 ) Healthy EC maintain homeostasis through a dynamic balance between expression of protective genes and repression of proinflammatory genes. Finally, mutation of the NF-B site at 188 resulted in loss of ICAM-1 up-regulation following Erg Genebloc, indicating that NF-B is involved in the Erg-dependent repression. https://doi.org/10.1038/s44161-022-00144-3, DOI: https://doi.org/10.1038/s44161-022-00144-3. Erg is the most highly expressed ETS factor in resting EC (7), where it acts as an activator of genes involved in homeostasis, including endoglin (8), ICAM-2 (9), vascular endothelial-cadherin (10), and heme oxygenase-1 (11). 2003;425(6958):57784. The role of Erg as a repressor of inflammation is in contrast to that of other ETS factors, which have previously been shown to act synergistically with NF-B in promoting inflammatory gene expression. Lab Invest. 5D, panel i), confirming that cIAP2 is repressed by Erg in resting HUVEC. 3C). 2022 Feb;102(2):204-211. doi: 10.1038/s41374-021-00698-z. (2010), Genome-wide analysis of ETS family DNA-binding, Wilson N. K., Foster S. D., Wang X., Knezevic K., Schtte J., Kaimakis P., Chilarska P. M., Kinston S., Ouwehand W. H., Dzierzak E., Pimanda J. E., de Bruijn M. F., Gttgens B. Proc Natl Acad Sci U S A. ETS-related Gene (ERG) Controls Endothelial Cell Permeability via Transcriptional Regulation of the Claudin 5 (CLDN5) Gene* ETS-related gene (ERG) is a member of the ETS transcription factor family. Erg levels are inhibited by TNF- stimulation (9, 13), and recently we have shown that overexpression of Erg inhibits TNF--induced NF-B activity. *, p < 0.05; **, p < 0.01. Overlapping ETS and NF-B binding sites have been identified in the regulatory regions of inflammatory genes such as IL-3, IL-12, IL-2, IL-2 receptor-, and granulocyte-macrophage colony stimulating factor (4952). An official website of the United States government. Adv Anat Embryol Cell Biol. Med Mol Morphol. Dustri-Verlag Dr. Karl Feistle GmbH & Co. KG. Essential roles of a variant NF-B site and p65 homodimers, Birdsey G. M., Dryden N. H., Shah A. V., Hannah R., Hall M. D., Haskard D. O., Parsons M., Mason J. C., Zvelebil M., Gottgens B., Ridley A. J., Randi A. M. (2012), The transcription factor Erg regulates expression of histone deacetylase 6 and multiple pathways involved in endothelial cell migration and angiogenesis, Zhang Y., Gavriil M., Lucas J., Mandiyan S., Follettie M., Diesl V., Sum F. W., Powell D., Haney S., Abraham R., Arndt K. (2008), IB kinase inhibitor IKI-1 conferred tumor necrosis factor sensitivity to pancreatic cancer cells and a xenograft tumor model, Sana T. R., Janatpour M. J., Sathe M., McEvoy L. M., McClanahan T. K. (2005), Microarray analysis of primary endothelial cells challenged with different inflammatory and immune cytokines, Barish G. D., Yu R. T., Karunasiri M., Ocampo C. B., Dixon J., Benner C., Dent A. L., Tangirala R. K., Evans R. M. (2010), Bcl-6 and NF-B cistromes mediate opposing regulation of the innate immune response, Prasad D. D., Rao V. N., Reddy E. S. (1992), Jeong B. C., Kim M. Y., Lee J. H., Kee H. J., Kho D. H., Han K. E., Qian Y. R., Kim J. K., Kim K. K. (2006), Brain-specific angiogenesis inhibitor 2 regulates VEGF through GABP that acts as a transcriptional repressor, Okada Y., Yano K., Jin E., Funahashi N., Kitayama M., Doi T., Spokes K., Beeler D. L., Shih S. C., Okada H., Danilov T. A., Maynard E., Minami T., Oettgen P., Aird W. C. (2007), A 3-kb fragment of the human Robo4 promoter directs cell type-specific expression in endothelium, Voraberger G., Schfer R., Stratowa C. (1991), Cloning of the human gene for intercellular adhesion molecule 1 and analysis of its 5-regulatory region. The The patient had an uneventful post-operative recovery. Embryos were harvested at E10.5 and yolk sac vasculature was analyzed by light microscopy and immunostaining. Furthermore, in 1 case of a GBM, CD34 stained not only endothelial cells, but also tumor cells. 8600 Rockville Pike In addition, immunostains for CD31, CD34, and -smooth muscle actin (-SMA) were performed on all samples. We show that Erg binds to both EBS 118 and EBS 181, the latter located within the NF-B binding site. Whether Erg represses NF-B target genes through recruiting these or other co-repressors is being investigated. Sci-Hub | Downregulation of ERG and FLI1 expression in endothelial cells triggers endothelial-to-mesenchymal transition. 43 the absence of. 2021. Table 1 lists the shared genes enriched in more than one study. Hyperglycemia is closely associated with prediabetes and Type 2 Diabetes Mellitus. 3N. Acta Neuropathol. Macrophage Sprouty4 deficiency diminishes sepsis-induced acute lung injury in mice. 21 in view of the widespread expression of the gm-csf receptor in the cerebral parenchyma, including the microglia, ependymal cells, choroid plexus cells, neurons, and endothelial cells, 18, Primers for site-directed mutagenesis are listed in supplemental Table S1. Before Common genes enriched for Erg GSEA among all three studies are in dark grey. Potential role of physical interactions between Elf-1, HMG-I(Y), and NF-B family proteins, Shiraya S., Miwa K., Aoki M., Miyake T., Oishi M., Kataoka K., Ohgi S., Ogihara T., Kaneda Y., Morishita R. (2006), Hypertension accelerated experimental abdominal aortic aneurysm through up-regulation of nuclear factor B and Ets, Goetze S., Kintscher U., Kaneshiro K., Meehan W. P., Collins A., Fleck E., Hsueh W. A., Law R. E. (2001), TNF induces expression of transcription factors c-, Hultgrdh-Nilsson A., Cercek B., Wang J. W., Naito S., Lvdahl C., Sharifi B., Forrester J. S., Fagin J. The Endothelial Transcription Factor ERG Mediates a Differential Role in the Aneurysmatic Ascending Aorta with Bicuspid or Tricuspid Aorta Valve: A Preliminary Study. The 3D invitro model of angiogenesis was performed as described previously (. 176, 19831998 (2010). Genome-wide analysis of 10 major transcriptional regulators, Regulatory elements and transcription factors controlling basal and cytokine-induced expression of the gene encoding intercellular adhesion molecule 1, Chen W., Bacanamwo M., Harrison D. G. (2008), Activation of p300 histone acetyltransferase activity is an early endothelial response to laminar shear stress and is essential for stimulation of endothelial nitric-oxide synthase mRNA transcription, Wang J. G., Mahmud S. A., Thompson J. Progressive loss of retinal ganglion cell axons - manifests as irreversible . MeSH B-cell lymphoblastoid cell lines, encoding 16 different DPB1 alleles, were studied. J. Pathol. Miettinen M, Wang ZF, Paetau A, Tan SH, Dobi A, Srivastava S, Sesterhenn I. All graphical data are SEM, Pericyte recruitment is a critical step in vascular stability and maturation, and lack of pericytes has been shown to cause increased permeability (. Disclaimer, National Library of Medicine Erg binds to ICAM-1 promoter through EBS 118 and 181, and NF-B p65 binds to EBS 181. Projects in the group focus on three main areas: - Transcriptional and epigenetic control of endothelial homeostasis by the ETS transcription factor ERG - von Willebrand Factor regulation of angiogenesis and angiodysplasia Federal government websites often end in .gov or .mil. Also, analysis of the genome-wide binding sites of 10 key regulators of blood stem/progenitor cells identified a combinatorial interaction between a heptad of transcription factors including Erg (29). After transduction with AdIBSR, the increase in ICAM-1 mRNA expression following Erg inhibition was lost, compared with cells transduced with AdlacZ (Fig. HES6, C-HAIRY1, HES-6, bHLHb41, bHLHc23, hes family bHLH transcription factor 6. 2000; 88: 26062618. The role of wnt signaling in physiological and pathological angiogenesis. We have previously shown that Erg binds to the ICAM-1 promoter (12). This smooth anticoagulant surface functions as a selective filter to regulate the passage of gases, fluid, immune cells, and various molecules. 5D, panel ii, and supplemental Fig. b: ERG exclusively, Figure 7.. EVI of different CNS lesions,. A potential mechanism for thrombosis in eosinophilic inflammatory states, Regulation of the human P-selectin promoter by Bcl-3 and specific homodimeric members of the NF-B/Rel family, Xue J., Thippegowda P. B., Hu G., Bachmaier K., Christman J. W., Malik A. National Library of Medicine The identification of key mediators to regain control of EC homeostasis has great potential for the development of novel therapeutics. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. This site is also responsible for the repression of ICAM-1 by the ETS factor FEV. Clipboard, Search History, and several other advanced features are temporarily unavailable. Liu J, Zhuang T, Pi J, Chen X, Zhang Q, Li Y, Wang H, Shen Y, Tomlinson B, Chan P, Yu Z, Cheng Y, Zheng X, Reilly M, Morrisey E, Zhang L, Liu Z, Zhang Y. Ets-1, Ets-2, and ERM overexpression in RK13 cells increased ICAM-1 promoter activity through EBS 118 (25). performed experiments and analyzed results. ChIP was carried out on a confluent monolayer of quiescent or TNF--treated HUVEC. The https:// ensures that you are connecting to the 2022 Dec;58:102513. doi: 10.1016/j.redox.2022.102513. Article J Pers Med. The emerging role of leptin in obesity-associated cardiac fibrosis: evidence and mechanism. In conclusion, the EMSA experiments indicate that Erg binds to both EBS 118 and 181 in the ICAM-1 promoter. Because Erg inhibits ICAM-1 expression by repressing NF-B activity, we hypothesized that Erg may also inhibit the expression of other NF-B target genes in resting endothelium. Members of the transcription factor family nuclear factor (NF)-B are important mediators of proinflammatory responses in the vasculature. Vascular morphogenesis: a Wnt for every vessel?. endothelial junctions are crucial for the maintenance and regulation of vascular homeostasis and function and mediate a complex signaling network. (A) 3D rendering of confocal microscopy images of whole-mount Matrigel plugs perfused with the dextran tracers. Therapeutic angiogenesis for cardiovascular disease: biological context, challenges, prospects. https://doi.org/10.1182/blood-2007-08-105346, https://doi.org/10.1038/s41569-019-0176-3, https://doi.org/10.1038/s41467-017-01169-0, 81470516 and 81530012/National Natural Science Foundation of China, 81700254/National Natural Science Foundation of China, 2018YFC1311300/National Key R&D Program of China, 2042018kf1032/Fundamental Research Funds for the Central Universities, 2042017kf0085/Fundamental Research Funds for the Central Universities, 2016ZX-008-01/Development Center for Medical Science and Technology National Health and Family Planning Commission of the People's Republic of China (The prevention and control project of cardiovascular disease). (2004), Ets ternary complex transcription factors, Wasylyk B., Hagman J., Gutierrez-Hartmann A. Briefly, biotinylated double-stranded oligonucleotides containing the ICAM-1 promoter sequence surrounding and including EBS 118 and 181 were incubated with 2 g of HUVEC nuclear lysate with or without excess unbiotinylated oligonucleotides. Thus, using two separate inhibitors of NF-B, we have demonstrated that the up-regulation of ICAM-1 after Erg inhibition is mediated by the activity of NF-B. An official website of the United States government. The utility of ERG, CD31 and CD34 in the cytological diagnosis of angiosarcoma: an analysis of 25 cases. official website and that any information you provide is encrypted Erg enrichment at R4, which includes EBS 118 and EBS 181, was greater than at other regions containing EBS (Fig. The site is secure. data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAKAAAAB4CAYAAAB1ovlvAAAAAXNSR0IArs4c6QAAAnpJREFUeF7t17Fpw1AARdFv7WJN4EVcawrPJZeeR3u4kiGQkCYJaXxBHLUSPHT/AaHTvu . One of the sites is within the NF-B consensus binding site, and our data suggest that Erg may directly compete with NF-B p65 for binding at this site. Showing cell line RNA expression of ERG (erg-3, p55). At the junctions, VE-cadherin binds -catenin, protecting it from degradation; this interaction is required for the control of junction stabilization (. Gene set enrichment analysis of transcriptome profiles of Erg and NF-B-dependent genes, together with chromatin immunoprecipitation (ChIP) studies, reveals that this mechanism is common to other proinflammatory genes, including cIAP-2 and IL-8. Chromatin immunoprecipitation (ChIP) was performed using ChIP-IT express (Active Motif, Rixensart, Belgium) as previously described (10). Constitutive Wnt signaling activation caused by mutations in -catenin or genes that control -catenin stability has been associated with aberrant cell proliferation and subsequent cancer progression (reviewed in. ERG is a critical regulator of Wnt/LEF1 signaling in prostate cancer. Four new HLA-DPB1 alleles were identified, DPB1*0502, DPB1*0602, DPB1*0802 and DPB1*0902, which have exon 2 sequences identical to other DPB1 alleles but differ in the . EBS were mutated from GGAA to CCAA. (A) Western blot of -catenin expression in control and ERG-deficient cells treated in presence or absence of MG132 (n= 4). Proliferation of vascular smooth muscle cells in glioblastoma multiforme. Advances knowledge of these transcription factors, in terms of structure, function . Figure 1.. Matlab quantitative determination of EVI., Figure 1.. Matlab quantitative determination of EVI. Epub 2020 Jul 3. NF-B activity was inhibited using an adenovirus expressing a mutant super repressor version of IB (AdIBSR), which cannot be phosphorylated and degraded, resulting in sequestration of NF-B in the cytoplasm (14). Epub 2021 Nov 13. Careers. Wnt targets CyclinD1 and Axin2, previously shown to be decreased in ERG-deficient endothelium (see. Comparison with genes up-regulated in TNF--treated endothelial cells gave a significant normalized enrichment score of 2.06 (Fig. One of the EBS (118) involved in Erg-mediated repression of ICAM-1 expression was previously shown to be required for the regulation of ICAM-1 in non-endothelial cells. C57BL/6 mice received a subcutaneous injection of Matrigel (BD Biosciences), as described (, Primary mouse lung EC were isolated from control, Primary HUVEC were harvested from umbilical cords (. I.M.A. The addition of an anti-Erg antibody resulted in a decrease in the intensity of the two upper bands, suggesting that Erg binds to this complex (Fig. No supershifted band was visible after the addition of the anti NF-B p65 antibody. # Discussion A hemangioma is a usually benign vascular tumor derived from blood vessel cell types. 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