erg endothelial cells

This smooth anticoagulant surface functions as a selective filter to regulate the passage of gases, fluid, immune cells, and various molecules. The new PMC design is here! We show that Erg binds to the promoters of a number of NF-B target genes, repressing their basal expression. The endothelial transcription factor ERG promotes vascular stability and growth through Wnt/-catenin signaling. Induction by cytokines and phorbol ester, Roebuck K. A., Rahman A., Lakshminarayanan V., Janakidevi K., Malik A. Med Mol Morphol. The identification of key mediators to regain control of EC homeostasis has great potential for the development of novel therapeutics. TCF reporter constructs TOPFLASH and FOPFLASH were used to measure the transcriptional activity of -catenin/TCF (. DNA protein interactions were then investigated using the Lightshift chemiluminescent EMSA kit (Pierce). (1995), de Launoit Y., Audette M., Pelczar H., Plaza S., Baert J. L. (1998), The transcription of the intercellular adhesion molecule-1 is regulated by Ets transcription factors, Yockell-Lelivre J., Spriet C., Cantin P., Malenfant P., Heliot L., de Launoit Y., Audette M. (2009), Functional cooperation between Stat-1 and ets-1 to optimize, Maurer P., T'Sas F., Coutte L., Callens N., Brenner C., Van Lint C., de Launoit Y., Baert J. L. (2003), FEV acts as a transcriptional repressor through its DNA-binding ETS domain and alanine-rich domain, Wei G. H., Badis G., Berger M. F., Kivioja T., Palin K., Enge M., Bonke M., Jolma A., Varjosalo M., Gehrke A. R., Yan J., Talukder S., Turunen M., Taipale M., Stunnenberg H. G., Ukkonen E., Hughes T. R., Bulyk M. L., Taipale J. The oligonucleotide containing EBS 118 formed a number of complexes with nuclear proteins from resting HUVEC (Fig. We also show that Erg blocks NF-B p65 binding to the promoters of ICAM-1, IL-8, and cIAP2 in resting HUVEC and that inhibition of Erg results in NF-B-mediated induction of the expression of these genes. (H) Luciferase reporter assay, an ERG cDNA expression plasmid (pcDNA-ERG), or an empty expression plasmid (pcDNA) were cotransfected with a Fzd4 promoter-luciferase construct (pGl4-Fzd4) in HUVEC and luciferase activity was measured. 8600 Rockville Pike Here we describe a novel mechanism that controls the activation of NF-B in EC. and transmitted securely. S3). Identification et impacts des anomalies gntiques dans la gense, l'volution clinique et le traitement des gliomes To confirm the specificity for Erg binding at this site, ChIP was carried out on chromatin from HUVEC treated with Erg siRNA. 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, Luscinskas (Harvard Medical School, Boston, MA) for providing the VE-cadherin GFP adenovirus; L. Lawrence (Imperial College London, UK) for technical assistance; G. Cossu (University of Manchester, UK) for critical reading of the manuscript; and A. Taddei (Cancer Research UK, London, UK), M. Johns (Imperial College London, UK), and D. Haskard (Imperial College London, UK) for helpful discussions. We show that constitutive endothelial deletion of ERG (, Angiogenesis is essential during embryogenesis and is a critical component of many diseases. Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization. Values are represented as the fold change in relative luciferase activity over the empty pGL4 vector alone. 2021 Jan 1;14(1):116-125. eCollection 2021. Interestingly, ERG overexpression in the invivo Matrigel plug model resulted in increased pericyte recruitment to vessels. We demonstrate that Erg binds to two ETS binding sites (EBS) in the ICAM-1 promoter and we show that both EBS and NF-B consensus sites are required for the repressive activity of Erg. (1998), Synergistic regulation of the human interleukin-12 p40 promoter by NFB and Ets transcription factors in Epstein-Barr virus-transformed B cells and macrophages, John S., Reeves R. B., Lin J. X., Child R., Leiden J. M., Thompson C. B., Leonard W. J. Caporarello N, Lee J, Pham TX, Jones DL, Guan J, Link PA, Meridew JA, Marden G, Yamashita T, Osborne CA, Bhagwate AV, Huang SK, Nicosia RF, Tschumperlin DJ, Trojanowska M, Ligresti G. Nat Commun. Mod Pathol. However, the EBS mutant constructs 118 and 181, and the combined 118/181 mutant, showed no significant increase in promoter activity after Erg Genebloc treatment compared with control Genebloc, indicating involvement of these sites in Erg-mediated repression of ICAM-1 promoter activity. sharing sensitive information, make sure youre on a federal Our data highlights for the first time a mechanism of combinatorial repression involving Erg and NF-B, controlling basal repression of ICAM-1 and other proinflammatory endothelial genes. Pisano C, Terriaca S, Scioli MG, Nardi P, Altieri C, Orlandi A, Ruvolo G, Balistreri CR. Adv Anat Embryol Cell Biol. Oligonucleotide sequences are listed in supplemental Table S1. List of shared genes enriched in more than one study. Adult endothelium cell fate is maintained by ERG and FLI1. Optimized fibrin gel bead assay for the study of angiogenesis. Regulation Of Endothelial Cell Migration; . After transduction with AdIBSR, the increase in ICAM-1 mRNA expression following Erg inhibition was lost, compared with cells transduced with AdlacZ (Fig. Shifted protein-oligonucleotide complexes are indicated by an arrow and super-shifted complexes are indicated by arrowhead. (A) Western blot of -catenin expression in control and ERG-deficient cells treated in presence or absence of MG132 (n= 4). RGC death occurs by apoptosis or necrosis. By inhibiting the activity of constitutive low levels of nuclear NF-B, Erg represses the transactivation of a set of proinflammatory NF-B target genes. In the retinal vasculature of littermate controls ( Ergfl/fl ), ERG was strongly expressed in endothelial cells (EC) from all regions of the vascular plexus, including tip and stalk cells, arteries, veins, and capillaries ( Figure S1 K), in line with previous studies ( Korn et al., 2014 ). As expected, inhibition of Erg expression by siRNA decreased the amount of Erg binding to the ICAM-1 promoter (see Fig. Furthermore, PGA-PTX-E-[c(RGDfK)2] blocked endothelial cells' migration towards vascular endothelial growth factor, and capillary-like tube formation, and inhibited endothelial cells' attachment to fibrinogen in the 4T1 breast tumor model. a: H & E demonstrates markedly diffuse microvascular proliferation. 2003; 3: 721732. 2019;16(8):491502. Genome-wide screen reveals WNT11, a non-canonical WNT gene, as a direct target of ETS transcription factor ERG. This is likely to be the result of endothelial activation by proinflammatory stimuli, because Erg levels have been shown to decrease upon LPS or TNF- stimulation (9, 13). 2022 Jul 25;13(1):4170. doi: 10.1038/s41467-022-31890-4. A method for rapid flow-cytometric isolation of endothelial nuclei and RNA from archived frozen brain tissue. 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. Nat Rev Cancer. Kalna, V. et al. PMC B., Tiruppathi C. (2009), NF-B regulates thrombin-induced ICAM-1 gene expression in cooperation with NFAT by binding to the intronic NF-B site in the ICAM-1 gene, Pierce J. W., Schoenleber R., Jesmok G., Best J., Moore S. A., Collins T., Gerritsen M. E. (1997), Novel inhibitors of cytokine-induced IB phosphorylation and endothelial cell adhesion molecule expression show anti-inflammatory effects, Subramanian A., Tamayo P., Mootha V. K., Mukherjee S., Ebert B. L., Gillette M. A., Paulovich A., Pomeroy S. L., Golub T. R., Lander E. S., Mesirov J. P. (2005), Gene set enrichment analysis. All graphical data are SEM, To investigate the role of ERG in physiological and pathological postnatal angiogenesis, floxed. Additionally, we mutated the NF-B site at 188, previously identified as important for cytokine-mediated up-regulation of ICAM-1 (15) (Fig. Mol Cell Biochem. Endothelial Cells. government site. In contrast, we observed that ERG was only expressed in the nuclei of endothelial cells, for example, in the hyperplastic vascular complexes that comprise the glomeruloid microvascular proliferation seen in GBMs. performed bioinformatic analysis and interpretation; and L.R. (2004), Ets ternary complex transcription factors, Wasylyk B., Hagman J., Gutierrez-Hartmann A. provided advice and contributed to scientific discussion; R.H.A. Disclaimer, National Library of Medicine Scale bar, 20m. Sequencing was carried out to confirm mutation of the desired EBS. A., Geng J. G., Key N. S., Slungaard A. https://doi.org/10.1038/s44161-022-00144-3. Combined genomic and antisense analysis reveals that the transcription factor Erg is implicated in endothelial cell differentiation. In endothelial cells (ECs), DHA reduces the cell proliferation, migration, and tube formation [6-8]. Blood. There were two labeled dextran molecules of different molecular weights, 210. Cooperative ETS transcription factors enforce adult endothelial cell fate and cardiovascular homeostasis. However, Erg overexpression repressed the EBS 118 and 181 constructs when these EBS were mutated individually (Fig. The role of EBS 118 in Erg repression of ICAM-1 activity, however, is less clear. INTRODUCTION HISTORY Results: Erg represses NF-B p65 . 3B), in fact p65 does not bind to this same sequence in native chromatin from unstimulated HUVEC. Get the most important science stories of the day, free in your inbox. NF-B activity is tightly regulated through feedback repressive mechanisms (3, 4). This is a preview of subscription content, access via your institution, Get immediate online access to Nature and 55 other Nature journal. . erg, which is highly enriched in ecs, and cldn5 have been identified to play an important role in inflammation-induced vascular dysfunction, leading to increased permeability. In the presence of bFGF (, Matrigel containing bFGF or VEGF with adenovirus expressing either Lacz (Ad.Lacz) or ERG (Ad.ERG) was injected into C57BL6 mice. 3C). OMIM: 610331 MGI: 1859852 HomoloGene: 23111 GeneCards: HES6. Previous studies have demonstrated that Erg binds to an EBS in the IL-8 promoter (13). Figure 7.. EVI of different CNS lesions, plotted with SD. S3). From the National Heart and Lung Institute (NHLI) Cardiovascular Sciences Unit, Hammersmith Hospital, Imperial College London, London W12 0NN and, the Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom. Common gene hits and accession numbers from GSEA analysis. (A) Representative whole mount images of E10.5, (B) Endomucin staining of blood vessels in E10.5, (C) Isolectin B4 staining of postnatal day 6 retinas from. Thus, these results show that although p65 can bind to the NF-B site within this region of the ICAM-1 promoter, when presented as an oligonucleotide, such as in the EMSA (Fig. Epub 2021 Feb 2. Images are a single representation of at least 3 separate experiments. 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. This article demonstrates the role of ERG in the control of vascular gene expression through epigenetic regulation of super-enhancers. (D, panels iii and iv) ChIP was carried out on sheared chromatin from HUVEC treated with control or Erg siRNA, using an anti NF-B p65 or control IgG antibody. The role of endothelial autocrine NRG1/ERBB4 signaling in cardiac remodeling. (E) (Top) Representative whole mount images of E10.5. These parent stem cells, ESCs, give rise to progenitor cells, which are . HHS Vulnerability Disclosure, Help You are using a browser version with limited support for CSS. Analysis of the three studies together suggests a strong correlation, although not complete overlap, between genes repressed by Erg and genes transactivated by NF-B. The site is secure. Online ahead of print. ICAM-1 mRNA levels were measured by quantitative RT-PCR and results are expressed as fold-change compared with control siRNA AdLacZ-treated. 2007; stem cells, and it has been suggested that these . 2004;101(11):391520. Crucial among these are the adhesion molecule vascular endothelial (VE)-cadherin and its intracellular partner -catenin, an essential component of the canonical Wnt pathway (reviewed in. Zhang, X., Hu, C., Yuan, Y.-P., Song, P., Kong, C.-Y., Wu, H.-M., Tang, Q.-Z. Addition of an anti-Erg antibody resulted in the appearance of a supershift (Fig. Epub 2019 Jun 10. Dufton NP, Peghaire CR, Osuna-Almagro L, Raimondi C, Kalna V, Chauhan A, et al. endothelial junctions are crucial for the maintenance and regulation of vascular homeostasis and function and mediate a complex signaling network. Ets-1, Ets-2, and ERM overexpression in RK13 cells increased ICAM-1 promoter activity through EBS 118 (25). Over the last decade, major progress has been made in understanding the molecular mechanisms that regulate angiogenesis. 2020 Aug 1;319(2):H443-H455. Would you like email updates of new search results? Baldus CD, Liyanarachchi S, Mrozek K, Auer H, Tanner SM, Guimond M, et al. ERG and nestin: useful markers of immature vessels and novel prognostic markers in renal cell carcinoma. Am. assisted in the design of the transgenic mice, provided reagents, advice, and contributed to scientific discussion; and A.M.R. All graphical data are SEM, Wnt ligands bind to receptors of the Fzd family to inhibit the -catenin degradation complex and activate Wnt signaling (. Before Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. This modality has been successfully applied to destruct ERG, a TF overexpressed in 50% of both primary and metastatic prostate cancer , and LEF1, another cancer-related TF involved in migration and invasion, with potent efficacy in cultured cells. Recently, we and others have shown that Erg represses endothelial expression of proinflammatory molecules ICAM-1 and IL-8 in quiescent cells, and that inhibition of Erg induces leukocyte adhesion to unstimulated human umbilical vein endothelial cells (HUVEC) (12, 13), suggesting an important role for Erg in maintaining EC homeostasis by repressing basal expression of proinflammatory genes. Cells were transfected with control pCMV6 or pCMV6-Fzd4 plasmids and transduced with VEC-GFP adenovirus (n= 3). Get time limited or full article access on ReadCube. To update your cookie settings, please visit the. Control of NF-B activity is essential to maintain quiescence and for the resolution of the inflammatory response; in chronic inflammation the tight control on NF-B is lost, leading to vascular diseases such as atherosclerosis (5). To evaluate the stability of the new vessels, vascular permeability was measured using two different sized dextran tracers. Internet Explorer). Dysfunctional ERG signaling drives pulmonary vascular aging and persistent fibrosis. 5B). Thus Erg provides a checkpoint to protect endothelial cells against inappropriate activation, and may prevent the onset of chronic inflammatory vascular diseases, such as atherosclerosis. Bifunctional role for VEGF-induced heme oxygenase-1 invivo: induction of angiogenesis and inhibition of leukocytic infiltration. Nuclear effectors of the Ras-MAP-kinase signaling pathway, Peter M., Couturier J., Pacquement H., Michon J., Thomas G., Magdelenat H., Delattre O. 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. Endothelial-to-mesenchymal transition (EndMT) is a phenomenon in which endothelial cells lose their characteristics and acquire mesenchymal-like properties. (I) TCF reporter (TOP) activity in control and ERG-deficient HUVEC treated with rWnt3a. *, p < 0.05; **, p < 0.01. The supershift was specific, as it was competed off by an excess of unlabeled probe, but not by unlabeled probe containing a mutation of the EBS 118 (Fig. Analysis of oligonucleotide screening and ChIP sequencing (ChIP Seq) data has suggested a possible specific Erg consensus motif of (A/C)GGAA(G/A) (28) or AGGA(A/T)(G/A) (29). Perfused vessels are labeled with FITC-dextran (green) and vessel leakage is visualized with TRITC-dextran (red). 8600 Rockville Pike 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. ERG knockdown causes spontaneously cardiac fibrosis and dysfunction. about navigating our updated article layout. Deletion of ERG disrupts regulation of coagulation, leading to a. Taken together, these data suggest that Erg repression involves two EBS, 118 and 181 bp upstream of the transcription start site and either of these sites is sufficient for Erg-mediated repression. [BMC Molecular and Cell Biology] Full Article Published In Prostate Cell News Kimble AL, Silva J, Omar OM, Murphy M, Hensel JA, Nicholas SE, Jellison ER, Reese B, Murphy PA. To further define the role of ERG in regulating EC function, we evaluated the effect of ERG knockdown on EC lumen formation in 3D collagen matrices. These data suggest that Erg may be important in maintaining endothelial quiescence and in the termination of the inflammatory response, by preventing the induction of proinflammatory gene expression. HHS Vulnerability Disclosure, Help The following day, cells were transduced with 100 multiplicity of infection of IB Super Repressor Adenovirus (AdIBSR) (14) or AdLacZ in serum-free M199 medium for 2 h before replacing with complete M199 medium. Wnt/beta-catenin signaling induces proliferation, survival and interleukin-8 in human endothelial cells. An official website of the United States government. and K.H.D. We observed significantly higher quantitative expression of ERG in HBs than in other CNS tumors. 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. In conclusion, the EMSA experiments indicate that Erg binds to both EBS 118 and 181 in the ICAM-1 promoter. VAT will be added later in the checkout.Tax calculation will be finalised during checkout. and ancillary testing results (attenuation of rods, and later cones, on the full-field electroretinogram (ERG) mainstay of diagnosis and constriction of the visual field on Goldmann perimetry (see image) . This showed that Erg binds to the promoter of cIAP2. 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. Using EMSA, we investigated whether, in resting HUVEC, p65 interacts with the NF-B site at 188, which overlaps with EBS 181. The sets of genes regulated by TNF- in both studies significantly overlapped with genes up-regulated by Erg inhibition, suggesting a specific alignment of Erg with NF-B regulatory pathways. N-cadherin mediates pericytic-endothelial interaction during brain angiogenesis in the chicken. In combination with the current therapy, SSA had potential to improve treatment effectiveness and to prevent cancer recurrence. Accordingly, the expression of ERG in 22Rv1 and C4-2B cells co-cultured with HUVEC was determined, respectively. Endothelial cells were selected by magnetic separation and plated in primary 96-well plates coated with fibronectin/gelatin in EGM-2 medium. Chen R, Cao C, Liu H, Jiang W, Pan R, He H, Ding K, Meng Q. Redox Biol. A and B, HUVEC were treated with siRNA for Erg, Fli-1, Ets-2, or GABP for 24 h; relative expression of Erg, Fli-1, Ets-2, and GABP mRNA (A) or ICAM-1 mRNA (B) was quantified by RT-PCR and expressed as relative to control siRNA treatment (Cont). The ETS transcription factor ERG drives expression of VE-cadherinand controls junctional integrity. The ETS (E-26 transformation-specific) transcription factor ERG (ETS-related gene) is essential for endothelial homeostasis, driving expression of lineage genes and repressing proinflammatory genes. 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. Depending on the tissue and organ, endothelial cells can vary from each other. In conclusion, this set of experiments indicates that Erg-mediated repression of ICAM-1 involves EBS 118 and EBS 181, which is located within the NF-B consensus sequence, and requires a functional NF-B binding site. 2022 Oct 10. doi: 10.1007/s11010-022-04562-6. 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 (. Res. Circulation. One of these sites (EBS 181) is located within the consensus binding site for NF-B. Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. a: H & E demonstrates a vascular lumen. EBS were mutated from GGAA to CCAA. 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). 2C). HES6. A, schematic diagram of ICAM-1 promoter mutant constructs. 2012; 181: 11261141. (A) 3D rendering of confocal microscopy images of whole-mount Matrigel plugs perfused with the dextran tracers. Cardiac endothelium communicates closely with adjacent cardiac cells by multiple cytokines and plays critical roles in regulating fibroblasts proliferation, activation, and collagen synthesis during cardiac fibrosis. Abstract:Endothelial cells (ECs) across ages and tissues are highly heterogeneous in developmental origins, structures, functions, and cellular plasticity. 1E). Retinas were collected at P6 and processed as described (. 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. 1C). Gene set enrichment analysis (GSEA) overlap studies were carried out using GSEA software version 2.0 (Broad Institute). The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. Xu P, Ge FH, Li WX, Xu Z, Wang XL, Shen JL, Xu AB, Hao RR. PGA-PTX-E-[c (RGDfK)2] inhibited the growth of avb3-expressing endothelial cells and several cancer cells. Nature 529, 316325 (2016). LiCl or NaCl (400mg/kg, dissolved in water) was injected IP into pregnant female mice at E8.5 and E9.5. government site. 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 (. Acute myeloid leukemia with complex karyotypes and abnormal chromosome 21: amplification discloses overexpression of APP, ETS2, and ERG genes. Deletion of either VEGF-A or VEGFR2 in endothelial cells regulates levels of Dll4 in tip cells and, in turn, Notch inhibition provides a feedback loop that reinforces expression of VEGF-A and C-X-C chemokine receptor type 4 (CXCR4), which stimulate endothelial sprouting and proliferation in the expanding vascular plexus [13 ]. Accepted: Careers, GUID:8A869C8F-3853-491A-A110-510F14AE82FC, GUID:2D4AA9B1-FE7D-4409-927B-871B06175846, GUID:31150988-E97C-4929-BD34-8F0C077575CA, Endothelium, Ets Family Transcription Factor, NF-B Transcription Factor, Transcription Repressor, Vascular Biology, Erg Transcription Factor, ICAM-1, Endothelial Homeostasis, Endothelial Quiescence, The NF-B family of transcription factors and its regulation, Hoffmann A., Levchenko A., Scott M. L., Baltimore D. (2002), The IB-NF-B signaling module. The different expression levels and activities of ETS factors highlights their important role in regulating inflammation. Nat. More importantly, we proved that endothelial ERG overexpression notably prevented pressure overload-induced cardiac fibrosis. (D) Vascular density of isolectin B4 stained branches in the central plexus, scale bar, 50m; quantification (n= 6). Dev. This site needs JavaScript to work properly. (F) Quantification of yolk sac vitelline vessel diameter. Bookshelf It is possible that some of the genes may be indirect targets of Erg; genomic ChIP sequencing of Erg DNA binding profiles will address this question. 3D Reconstruction of Neovessels inside Matrigel Plugs Supplemented with VEGF and Adenovirus Expressing ERG, Related to Figure6. 1E). . Rafii, S., Butler, J. M. & Ding, B.-S. Angiocrine functions of organ-specific endothelial cells. Loss of ERG expression is associated with diseases including atherosclerosis. Fibrosis in the liver: Fibrosis. Am J Pathol. This article underscores the importance of ERG during vascular development and links vascular stability with the control of WNT signaling in the endothelium. An official website of the United States government. To investigate whether Erg is binding directly to EBS 118 or 181, we studied the interaction between Erg and these sequences by electrophoretic mobility shift assay (EMSA). Epub 2014 Oct 28. 2001;161:III-XIII, 1-151. doi: 10.1007/978-3-642-56553-3. All prices are NET prices. We therefore investigated whether NF-B is responsible for the up-regulation of ICAM-1 expression after Erg inhibition. Embryonic Pericytes Promote Microglial Homeostasis and Their Effects on Neural Progenitors in the Developing Cerebral Cortex. Single cell type. Nat Commun. 2017 Apr;95(4):445-460. doi: 10.1007/s00109-016-1504-2. b: ERG, Figure 4.. GBM, epithelioid type. Little is known about the maintenance of endothelial cell fate in adults. Erg expression was inhibited using either Genebloc (Silence Therapeutics AG, Berlin, Germany) as previously described (10), or by RNA interference with short interfering RNA (siRNA). Asano, Y. et al. Dark-adapted ERGs recordings showing ERG responses to dim and bright flashes in Gnat1 / . pGL4 ICAM-1 1.3 was mutated in either single or double EBS or in the NF-B binding site. 3D Reconstruction of Neovessels inside Matrigel Plugs Supplemented with VEGF and Adenovirus Expressing Lacz, Related to Figure6, Movie S2. 2022 Jan 19;42(3):362-376. doi: 10.1523/JNEUROSCI.1201-21.2021. Results show additional HLA-DPB1 polymorphism in exons 1, 3, 4 and 5 and the 5' and 3'-UTR. Evidence for an inducible autoregulatory pathway, Obesity, inflammation, and atherosclerosis, Karim F. D., Urness L. D., Thummel C. S., Klemsz M. J., McKercher S. R., Celada A., Van Beveren C., Maki R. A., Gunther C. V., Nye J. Numerous studies have shown that the new vasculature induced by VEGF invivo, to promote revascularization in ischemic diseases (. (B) ERG (magenta), VEC (red), -cat (green), and DAPI (blue) staining of control and ERG-deficient HUVEC transduced with GFP-tagged control (Ctrl-GFP) or VE-cadherin (VEC-GFP) adenovirus. 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-. See this image and copyright information in PMC. b: ERG exclusively, Figure 6.. Metastatic carcinoma. Analysis of the promoter sequences of other genes highlighted in the GSEA identified putative Erg binding sites within a distance equivalent to 12 nucleosomes away from an NF-B site.3 The involvement of distant sites in transcriptional repression has been well described, and may involve recruitment of co-repressors and/or modification of chromatin structure (41). Data are expressed as fold-change compared with IgG normalized to input and control region (n = 8). 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). ChIP was carried out on a confluent monolayer of quiescent or TNF--treated HUVEC. A, Erg siRNA or control siRNA-treated HUVEC were transduced with AdIBSR or AdLacZ. G.M.B. Requirement of a GT box (Sp1 site) and two Ets binding sites for vascular endothelial cadherin gene transcription. a: H & E demonstrates pseudopalisading cells surrounding areas of central necrosis,, Figure 3.. GBM, glomeruloid type. Google Scholar. Careers. 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. Other ETS combinatorial transcription factor motifs include the serum response elements that bind ternary complex ETS factors and the serum response factor (45), and ETS:AP1 binding motifs (46). November 10, (1998), Ets transcription factors. Our data shows that Erg inhibits NF-B p65 binding to the ICAM-1 promoter in quiescent EC. Nat Cardiovasc Res 1, 880881 (2022). Dev. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Erg is a member of the ETS family of transcription factors, characterized by a conserved ETS DNA binding domain that binds to a core consensus motif of GGA(A/T) (6). provided advice on retina isolation and optimized ERG retinal staining; E.D. The Wnt/beta-catenin pathway modulates vascular remodeling and specification by upregulating Dll4/Notch signaling. Circ. Erg binds to ICAM-1 promoter through EBS 118 and 181, and NF-B p65 binds to EBS 181. In addition, we also used GSEA to compare the Erg-regulated genes with the data from a recent ChIP seq analysis, which identified regulatory sequences bound by NF-B p65 in LPS-treated macrophages (19). (C) Western blot (left) and quantification (right) of -catenin expression in nuclear/cytoplasmic fractions of ERG-deficient HUVEC transduced with GFP or VEC-GFP adenovirus in presence or absence of LiCl. See supplemental Table S1 for oligonucleotide sequences. Temporal control and selective gene activation, Sun S. C., Ganchi P. A., Ballard D. W., Greene W. C. (1993), NF-B controls expression of inhibitor IB. Am J Physiol Heart Circ Physiol. A.V.S. This is a summary of: Gomez-Salinero, G. M. et al. Chromatin was enriched with an NF-B p65 antibody and binding sites were analyzed by quantitative PCR, using the ICAM-1 promoter primers described above (see Fig. Typically only the nuclei are visible, at the boundary between the lumen and the wall of a vessel. designed and carried out invitro experiments, analyzed, interpreted, and conceptualized results, and wrote the manuscript. Overlapping and divergent signaling pathways of N-cadherin and VE-cadherin in endothelial cells. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. Tight control of NF-B activation is crucial to cellular homeostasis, and several mechanisms, both at the transcriptional and non-transcriptional levels, have been identified. Publishers note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. 2005 Mar;38(1):36-42. doi: 10.1007/s00795-004-0273-0. Common genes enriched for Erg GSEA among all three studies are in dark grey. There are various types of hemangiomas. Dapper 1 antagonizes Wnt signaling by promoting dishevelled degradation. MeSH CD31 demonstrated variable and sometimes weak immunoreactivity for endothelial cells. Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis. September 24, Canonical Wnt signaling promotes EC survival, junction stabilization, proliferation, and pericyte recruitment and is essential for vessel stability (. Coordination of growth and stability signals is required for effective angiogenesis (. and transmitted securely. ChIP on resting HUVEC treated with control or Erg siRNA showed that NF-B p65 binding to the IL-8 and cIAP2 promoters increases significantly after Erg inhibition (Fig. ERG; Endothelial cells; Endothelin-1; Fibroblasts; Paracrine. The laboratory investigates the molecular pathways that regulate endothelial homeostasis, angiogenesis and vascular stability. 5C), indicating a trend toward a correlation. A, and B, biotinylated oligonucleotides containing sequences from the ICAM-1 promoter EBS 118 (A) or the EBS 181 (B) were incubated with nuclear lysate from resting HUVEC. This site needs JavaScript to work properly. Endothelial cell-derived non-canonical Wnt ligands control vascular pruning in angiogenesis. This work was funded by grants from the British Heart Foundation (PG/09/096 and RG/11/17/29256). ERG-dependent gene targets and pathways in the endothelium ERG regulates the expression of multiple EC genes with roles in key cellular functions such as survival, junction stability and cell migration; acting as a key regulator of endothelial homeostasis. A. A. Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. *, p < 0.05; **, p < 0.01; ***, p < 0.001. 1 The transcriptional mechanisms regulating EC lineage identity and maintenance of endothelial homeostasis are also areas of immense interest for vascular regenerative therapies but remain poorly understood. Thank you for visiting nature.com. Transcription cofactor HES-6 is a protein that in humans is encoded by the HES6 gene. These cells capture visual information and ultimately respond to light . Only one construct, containing mutation of the combined EBS 118 and 181, was not repressed by AdErg transduction. a: H & E demonstrates a vascular lumen. (2002), Molecular cloning of ESET, a novel histone H3-specific methyltransferase that interacts with ERG transcription factor, Yang L., Mei Q., Zielinska-Kwiatkowska A., Matsui Y., Blackburn M. L., Benedetti D., Krumm A. A role for the beta-catenin/T-cell factor signaling cascade in vascular remodeling. Res. A new DNA-binding motif that recognizes a purine-rich core DNA sequence, Hollenhorst P. C., Jones D. A., Graves B. J. ISSN 2731-0590 (online). C, ICAM-1 promoter activity of EBS mutants after AdErg treatment, expressed as luciferase activity relative to AdLacZ (n = 37). However, the pathways that control vessel stability are less well characterized. 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. ETS-related gene (ERG) is a transcription factor that has been linked to angiogenesis. Results are expressed as fold-change compared with IgG normalized to input and negative control region. 2017;8(1):895. Caught up in a Wnt storm: Wnt signaling in cancer. Federal government websites often end in .gov or .mil. ERG knockdown causes spontaneously cardiac fibrosis and dysfunction. 2014, Received in revised form: In endothelial cells (EC), the transcription factor NF-B is important in the switch from quiescence to activation, and is tightly controlled to avoid excessive inflammation and organ damage. The site is secure. For Apelin expression assay, cells were cultured in the presence of both 4-hydroxytamoxifen and recombinant human VEGF. (F) TCF reporter activity (TOP) in control and ERG-deficient cells treated with control (Ctrl), Wnt3a, or Wnt5a conditioned medium (CM); (n= 3). 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. We thank Dr. Odile Dumont, Dr. Richard Starke, Professor Guido Franzoso, Dr. Paul Evans, Professor Malcolm Parker, and Dr. Irina Udalova (Imperial College London) for discussions. 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). ( C) Endothelial cells ERG positive. Here we describe a novel mechanism that controls the activation of NF-B in EC. Keywords: Nature. HUVEC were seeded onto 1% gelatin-coated plates and grown in EGM-2 medium (Lonza, Wokingham, United Kingdom). Endothelial stem cells (ESCs) are one of three types of stem cells found in bone marrow.They are multipotent, which describes the ability to give rise to many cell types, whereas a pluripotent stem cell can give rise to all types. S1 and Ref. (F) There are three putative ERG binding sites (black bars) located within the Fzd4 locus upstream of the transcription start site (arrow); sequence conservation between 100 vertebrates is shown across this region. Endothelial cell-derived endothelin-1 promotes cardiac fibrosis in diabetic hearts through stimulation of endothelial-to-mesenchymal transition. Dysregulation of the Wnt/-catenin signaling pathway is frequently observed in many types of cancer. He was discharged from our hospital on postoperative day 6. ERG is abundant in murine hearts, especially in cardiac ECs, but decreased during fibrotic remodeling. (1997), A new member of the ETS family fused to EWS in Ewing tumors, Carrre S., Verger A., Flourens A., Stehelin D., Duterque-Coquillaud M. (1998), Erg proteins, transcription factors of the Ets family, form homo-, heterodimers, and ternary complexes via two distinct domains, Gottschalk L. R., Giannola D. M., Emerson S. G. (1993), Molecular regulation of the human IL-3 gene. The content on this site is intended for healthcare professionals. We selected the following ETS factors, all expressed in resting HUVEC, although at lower levels than Erg (supplemental Fig. Xl erg: expression pattern and overexpression during development plead for a role in endothelial cell differentiation. Endothelial Forkhead Box Transcription Factor P1 Regulates Pathological Cardiac Remodeling Through Transforming Growth Factor-1-Endothelin-1 Signal Pathway. 12 was mutated within ETS binding sites (EBS), or within the NF-B binding site as previously shown (15), using the QuikChange lightning multi site-directed mutagenesis kit (Agilent), all primers were designed using the QuikChange Primer Design Program (Agilent). In this study, Erg was shown to interact with two EBS in the ICAM-1 promoter, and both were found to be required for Erg repression of ICAM-1 expression. 1B), indicating that repression of ICAM-1 expression is not a shared property of constitutive ETS factors. EIF5 EIF6 ELF2 ELK1 ELK3 EMC8 EME1 EMG1 ENKD1 ENO3 ENTR1 ENY2 EOGT EP400P1 EPB41 EPB41L1 EPB41L2 EPB41L4A EPB41L5 EPHA2 EPHB4 EPS8L2 ERC1 ERCC1 ERG ERH ERMN ERVFRD-1 ESRRG ETFB ETHE1 ETNPPL ETS1 ETV3 ETV4 ETV5 EVI2A EXOC3 EXOC6 EXOSC1 EXOSC3 EXOSC7 F12 FAAH2 FAAP100 . 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 . E26 transformation-specific (ETS)-related gene (ERG) belongs to the ETS transcriptional factor family and is required for endothelial cells (ECs) homeostasis and cardiac development. As shown above, Erg repression of the ICAM-1 promoter requires EBS 181, which is part of the NF-B consensus sequence. Hypoxia is implicated in loss of retinal ganglion cells (RGCs) occurring in such conditions. A knowledge-based approach for interpreting genome-wide expression profiles, Subramanian A., Kuehn H., Gould J., Tamayo P., Mesirov J. P. (2007), GSEA-P, a desktop application for Gene Set Enrichment Analysis, Mootha V. K., Lindgren C. M., Eriksson K. F., Subramanian A., Sihag S., Lehar J., Puigserver P., Carlsson E., Ridderstrle M., Laurila E., Houstis N., Daly M. J., Patterson N., Mesirov J. P., Golub T. R., Tamayo P., Spiegelman B., Lander E. S., Hirschhorn J. N., Altshuler D., Groop L. C. (2003), PGC-1-responsive genes involved in oxidative phosphorylation are coordinately down-regulated in human diabetes, Furusu A., Nakayama K., Xu Q., Konta T., Sugiyama H., Kitamura M. (2001), Expression, regulation, and function of inhibitor of apoptosis family genes in rat mesangial cells, Strieter R. M., Kunkel S. L., Showell H. J., Remick D. G., Phan S. H., Ward P. A., Marks R. M. (1989), Endothelial cell gene expression of a neutrophil chemotactic factor by TNF-, LPS, and IL-1, Payankaulam S., Li L. M., Arnosti D. N. (2010), Transcriptional repression. ESCs have the characteristic properties of a stem cell: self-renewal and differentiation. Background: In quiescent endothelial cells, the transcription factor Erg regulates cell homeostasis by repressing expression of proinflammatory genes. Epub 2017 Jan 13. We observed that ERG was abundant in murine hearts, especially in cardiac ECs, but decreased during cardiac fibrosis. There was no recurrence at the 1-year follow up. -, Louis DN Ohgaki H Wiestler OD Cavenee WK Burger PC Jouvet A Scheithauer BW Kleihues P The 2007 WHO classification of tumours of the central nervous system. Zhou N, Ye Y, Wang X, Ma B, Wu J, Li L, Wang L, Wang DW, Zou Y. J Mol Med (Berl). 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. C, analysis of 1.3 kb of the ICAM-1 promoter identified putative EBS, Erg consensus sites, AP1/ETS sites, and an NF-B site as indicated. Crucially, we demonstrate that overexpression ofERG invivo enhances vascular endothelial growth factor (VEGF)-dependent angiogenesis and promotes stability of VEGF-induced new blood vessels. provided funding, conceived, designed, and supervised the study, interpreted results, and wrote the manuscript. The ICAM-1 promoter construct pGL4 ICAM-1 1.3 containing the first 1.3 kb upstream from the transcription start site as described in Ref. In summary, the data in this study describe a novel mechanism controlling endothelial homeostasis, based on the transcription factor Erg, and suggest a novel pathway of inhibition of NF-B activity in resting endothelium. 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). Erg levels are inhibited by TNF- stimulation (9, 13), and recently we have shown that overexpression of Erg inhibits TNF--induced NF-B activity. Besides, GATA3 is also a positive transcription factor regulating the expression of vWF [31, 32]. HES6, C-HAIRY1, HES-6, bHLHb41, bHLHc23, hes family bHLH transcription factor 6. An official website of the United States government. Anal Cell Pathol (Amst). volume1,pages 880881 (2022)Cite this article. We then carried out a separate GSEA between the whole Erg dataset and these two studies. 3D). To confirm the relationship between ERG and -catenin pathways, we used gene set enrichment analysis (GSEA) to compare the data set from transcriptome profiling of ERG-deficient HUVEC (, Since ERG inhibition decreases -catenin protein, but not mRNA levels, we tested whether ERG regulates -catenin degradation. official website and that any information you provide is encrypted In support of the specificity of the interaction of Erg with this site, addition of control IgG antibodies had no effect on the band pattern (Fig. provided reagents and contributed to scientific discussion; J.C.M. Activation of the NF-B pathway leads to the expression of multiple genes involved in inflammation, including cytokines and chemokines, adhesion molecules and growth factors. 2022 Sep 16;23(18):10848. doi: 10.3390/ijms231810848. HUVEC were isolated and cultured in supplemented M199 media as previously described (10). Mouse melanoma B16F0 tumors were grown in tamoxifen-treated adult. Bookshelf The 3D invitro model of angiogenesis was performed as described previously (. and JavaScript. This article contains supplemental Table S1 and Figs. (F) Quantification of pericyte coverage, pixel intensity (n= 8). The ETS transcription factor family is implicated in vascular development and angiogenesis (reviewed in. Finally, in this study, we explore the potential for ERG in promoting vascular stability during VEGF-induced angiogenesis. Briefly, sheared chromatin from HUVEC untreated, or treated with Erg or control siRNA, was fixed in 1% formaldehyde for 10 min before shearing chromatin using a Bioruptor (Diagenode, Liege, Belgium). To test the functional relevance of Wnt signaling in ERG-dependent angiogenesis, we used an invitro sprouting assay (. Article Members of the transcription factor family nuclear factor (NF)-B are important mediators of proinflammatory responses in the vasculature. 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 Immunoprecipitated DNA was analyzed by qPCR for primers covering ICAM-1 promoter regions 15 (D) or region 4 only (E) and negative control region. These results identify a role for Erg as a gatekeeper controlling vascular inflammation, thus providing an important barrier to protect against inappropriate endothelial activation. In the latest study, researchers found that loss of function of this ERG master gene in endothelial cells caused damage and fibrosis in the livers of mice. The Endothelial Transcription Factor ERG Mediates a Differential Role in the Aneurysmatic Ascending Aorta with Bicuspid or Tricuspid Aorta Valve: A Preliminary Study. There are very few reports of primary venous hemangiomas in the literature. Cross sectioning through neovessels (right) shows localization of the tracers. (E) EC sprouts at the angiogenic front (arrows), scale bar, 100m; quantification (n= 6). Although EndMT is observed in various diseases including cancer, and augments fibrosis and vascular defects, the mechanism of EndMT induction is not fully understood. 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. 16656 Ensembl ENSG00000127124 ENSMUSG00000028634 UniProt Q5T1R4 A2A884 RefSeq (mRNA) NM_001127714 NM_024503 NM_010657 RefSeq (protein) NP_001121186 NP_078779 NP_034787 Location (UCSC) Chr 1: 41.51 - 42.04 Mb Chr 4: 119.59 - 120 Mb PubMed search Wikidata View/Edit Human View/Edit Mouse Transcription factor HIVEP3 is a protein that in humans is encoded by the HIVEP3 gene. (A) Invitro Brdu incorporation in control and ERG-deficient HUVEC treated in presence or absence of LiCl (n= 4). Han E, Kim J, Jung MJ, Chin S, Lee JH, Won KY, Moon A. Int J Clin Exp Pathol. 1C). Provided by the Springer Nature SharedIt content-sharing initiative, Nature Cardiovascular Research (Nat Cardiovasc Res) S3) and negative control GAPDH promoter region. We carried out an initial screen to identify any overlap between genes up-regulated following Erg inhibition and published datasets held in the Broad Institute curated GSEA MSigDB database. AC, GSEA was carried out using standard settings. In quiescent EC, nuclear-localized NF-B p65 appears to have a role in constitutive expression of genes, such as ICAM-2 and P-selectin, as mutation of the NF-B binding sites within the promoters of these genes results in a decrease in basal activity (9, 33). 3B, lanes 2 and 3). We have previously shown that Erg binds to the ICAM-1 promoter (12). # Discussion A hemangioma is a usually benign vascular tumor derived from blood vessel cell types. In agreement with previous data, transduction with AdErg repressed ICAM-1 promoter activity to 38% of treatment with AdLacZ (Fig. Nuclear lysates from a confluent monolayer of HUVEC were extracted using the Nuclear extract kit (Active Motif) following the manufacturer's instructions. MB), Help with FEV expression is restricted to prostate and small intestine tissue (47) and Dami megakaryocytic cells (27). The above data suggest that Erg is repressing ICAM-1 through a mechanism that involves EBS 118 and EBS 181. Disruption of PPAR/-catenin-mediated regulation of apelin impairs BMP-induced mouse and human pulmonary arterial EC survival. EBS 181 is part of an NF-B consensus sequence that is bound by NF-B p65 after TNF- stimulation in HUVEC (15, 30). (D and E) (D) Western blot and (E) qPCR analysis of -catenin expression in control (siCtrl) and ERG-deficient (siERG) HUVEC (n= 4). Fibroblast growth factor 7 releasing particles enhance islet engraftment and improve metabolic control following islet transplantation in mice with diabetes. Therefore both genes are candidates for regulation by both Erg and NF-B. ERG silence in HUVECs promotes the secretion of endothelin-1, which in turn activates cardiac fibroblasts in a paracrine manner. 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 These data indicate that Erg binds to the ICAM-1 promoter in a region detected by the R4 primers, 188 to 103 bp upstream of the transcription start site. S3) and a negative control GAPDH promoter region. ERG is a member of the ETS transcription factor family that is highly enriched in endothelial cells (ECs). (2003), Responses to the proinflammatory cytokines interleukin-1 and tumor necrosis factor in cells derived from rheumatoid synovium and other joint tissues involve nuclear factor B-mediated induction of the Ets transcription factor ESE-1, Creative Commons Attribution Non-Commercial License. In the meantime, to ensure continued support, we are displaying the site without styles B.G. Cell 32, 8296 (2015). Inhibition of Erg expression increased the activity of the ICAM-1 promoter luciferase construct; conversely, overexpression of Erg by adenovirus (AdErg) repressed basal promoter activity. The https:// ensures that you are connecting to the Quantitative evaluation with automated methodology and custom Matlab 2008b software was used to calculate percent staining of ERG in each case. Collectively, endothelial ERG alleviates cardiac fibrosis via blocking ET-1-dependent paracrine mechanism and it functions as a candidate for treating cardiac fibrosis. This study aims at investigating the potential role and molecular basis of ERG in fibrotic remodeling within the adult heart. L.O.A. image, Download .pdf (5.91 These results demonstrate that endothelial ERG controls embryonic vascular development and angiogenesis through the Wnt/-catenin signaling pathway. Careers. n = 6 (B), n = 5 (C), *, p < 0.05; **, p < 0.01; ***, p < 0.001. data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAKAAAAB4CAYAAAB1ovlvAAAAAXNSR0IArs4c6QAAAnpJREFUeF7t17Fpw1AARdFv7WJN4EVcawrPJZeeR3u4kiGQkCYJaXxBHLUSPHT/AaHTvu . 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. 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). The .gov means its official. (BD) (B) Representative images of EC sprouts on fibrin gel beads using siCtrl or siERG-treated HUVEC in the presence or absence of LiCl; (C) quantification of numbers of sprouts; and (D) tube length (n= 20). The inhibitory activity of AdIBSR on NF-B was confirmed on TNF--stimulated HUVEC (supplemental Fig. You will then receive an email that contains a secure link for resetting your password, If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password. Dhaun N, Webb DJ. 2 erg has been recently studied immunohisto-chemically in prostate carcinoma, subsets of which have oncogenic tmprss2-erg gene fusions This consensus sequence appears in the ICAM-1 promoter five times, at 1239, 1136, 773, 118, and 75 relative to the transcription start site (Fig. 1D). (D and E) (D) qPCR and (E) western blot analysis of Fzd4 expression in control and ERG-deficient cells (n= 3). Dustri-Verlag Dr. Karl Feistle GmbH & Co. KG. a: H & E demonstrates glomeruloid microvascular proliferation. . 2019 Aug 20;140(8):665-680. doi: 10.1161/CIRCULATIONAHA.119.039767. Int J Mol Sci. These observations are in line with a previous report where global deletion of a subset of endothelial ERG isoforms resulted in vascular defects and lethality between E10.5 and E11.5 (. Primers for a downstream region within the Fzd4 gene were used as a negative control. 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 . (F) Representative images of B16F0 tumors which were grown for 14days on adult. Conversely, -SMA immunoreactivity was identified in the abluminal cells of these hyperplastic vessels. The recent years have witnessed an increased activity in biocompatibility research aimed at limiting biomaterial-induced blood coagulation. Epub 2021 Nov 13. Dynamic regulation of canonical TGFbeta signalling by endothelial transcription factor ERG protects from liver fibrogenesis. ERG and FLI1, induces EndMT coupled with dynamic . For long time, with the exception of ligand-inducible nuclear receptors, transcription factors were considered as "undruggable" targets. 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