A., Taborsky G. J., Jr., Chansky H. A. 2C). 8600 Rockville Pike The site is secure. Comparative genomic analysis of the Fzd4 promoter revealed the presence of three highly conserved ERG DNA binding motifs in the 800 base pair (bp) region upstream of the Fzd4 transcription start site (, Wnt/-catenin signaling can promote EC proliferation (. Am. Cooperative ETS transcription factors enforce adult endothelial cell fate and cardiovascular homeostasis. 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. image, Download .pdf (5.91 Finally, in this study, we explore the potential for ERG in promoting vascular stability during VEGF-induced angiogenesis. 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. Progressive loss of retinal ganglion cell axons - manifests as irreversible . (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) (. National Library of Medicine Sequencing was carried out to confirm mutation of the desired EBS. 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. From 2008 to 2016, a total of $36 946 764.00 USD has . Androgen receptor levels identification were detected in qRT-PCR and Western blot assay. Location of qPCR amplicon covering region R1 is indicated. In conclusion, the EMSA experiments indicate that Erg binds to both EBS 118 and 181 in the ICAM-1 promoter. 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. 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. The inhibitory activity of AdIBSR on NF-B was confirmed on TNF--stimulated HUVEC (supplemental Fig. 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. sharing sensitive information, make sure youre on a federal Copyright 2022 Elsevier Inc. except certain content provided by third parties. Collectively, endothelial ERG alleviates cardiac fibrosis via blocking ET-1-dependent paracrine mechanism and it functions as a candidate for treating cardiac fibrosis. Using the inducible endothelial specific Cdh5(PAC)-iCreERT2 line, we show that ERG is required for angiogenesis in the developing retina of newborn mice and for tumor blood vessel growth in adult mice. Addition of IgG antibodies had no effect on the band pattern (Fig. (2006), The principal eosinophil peroxidase product, HOSCN, is a uniquely potent phagocyte oxidant inducer of endothelial cell tissue factor activity. The identification of key mediators to regain control of EC homeostasis has great potential for the development of novel therapeutics. These results demonstrate that endothelial ERG controls embryonic vascular development and angiogenesis through the Wnt/-catenin signaling pathway. Claudin 4 identifies a wide spectrum of epithelial neoplasms and represents a very useful marker for carcinoma versus mesothelioma diagnosis in pleural and peritoneal biopsies and effusions 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. Additionally, we mutated the NF-B site at 188, previously identified as important for cytokine-mediated up-regulation of ICAM-1 (15) (Fig. 3B, lanes 46, arrows), suggesting that the anti-NF-B p65 antibody binds to the protein-oligonucleotide complex at this site. Endothelial cells were selected by magnetic separation and plated in primary 96-well plates coated with fibronectin/gelatin in EGM-2 medium. Using EMSA, we investigated whether, in resting HUVEC, p65 interacts with the NF-B site at 188, which overlaps with EBS 181. A new DNA-binding motif that recognizes a purine-rich core DNA sequence, Hollenhorst P. C., Jones D. A., Graves B. J. One of these sites (EBS 181) is located within the consensus binding site for NF-B. Mod Pathol. We therefore investigated whether NF-B is responsible for the up-regulation of ICAM-1 expression after Erg inhibition. June 13, 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. Cell sorting and proliferation assays performed after sustained ERG knockdown indicate that ERG drives proliferation and blocks the differentiation of prostate cells to both NE and luminal cell types. The site is secure. Chromatin was immunoprecipitated with 2 g antibody to Erg (sc-353, Santa Cruz Biotechnology, Inc), NF-B p65 (ab7970, AbCam, Cambridge, United Kingdom), or negative control rabbit IgG (PP64, Chemicon, Millipore). (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. The .gov means its official. and K.H.D. Epub 2019 Jun 10. Endothelial cell (EC) plasticity in pathological settings has recently been recognized as a driver of disease progression. n = 6 (B), n = 5 (C), *, p < 0.05; **, p < 0.01; ***, p < 0.001. ICAM-1 promoter activity is repressed after Erg overexpression in HUVEC (12); therefore we investigated whether this repression was lost after mutation of EBS in the ICAM-1 promoter. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. 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. S3) and a negative control GAPDH promoter region. 2014, Received: 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 1E). Results are expressed as fold-change compared with IgG normalized to input and negative control region. Han E, Kim J, Jung MJ, Chin S, Lee JH, Won KY, Moon A. Int J Clin Exp Pathol. 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. (1998), Ets transcription factors. The utility of ERG, CD31 and CD34 in the cytological diagnosis of angiosarcoma: an analysis of 25 cases. (1990), The ETS domain. (I) TCF reporter (TOP) activity in control and ERG-deficient HUVEC treated with rWnt3a. 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. Hattori Y, Itoh H, Tsugawa Y, Nishida Y, Kurata K, Uemura A, Miyata T. J Neurosci. FOIA 2007; stem cells, and it has been suggested that these . 3D). Epub 2013 Sep 27. 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). Alternatively, after 42 h following adenovirus transduction, cells were treated with 10 ng/ml of TNF- for 6 h. ICAM-1 mRNA levels were assessed by quantitative RT-PCR, normalized to GAPDH. Here, endothelial cells are of tremendous importance for the exchange of substances including oxygen, water, and lipids, as well as in the transfer of carbon dioxide and urea from a tissue to a vessel, and vice versa. G.M.B. Fibroblast growth factor 7 releasing particles enhance islet engraftment and improve metabolic control following islet transplantation in mice with diabetes. 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. To confirm that Erg repression of NF-B activation is a common mechanism in resting EC, we focused on two genes: cellular inhibitor of apoptosis (cIAP)-2 and IL-8. Hypoxia is implicated in loss of retinal ganglion cells (RGCs) occurring in such conditions. HUVEC were seeded at 3 104 per well in EGM-2 medium (Lonza) on a gelatin-coated 24-well plate, and the following day either transduced with AdErg or AdLacZ (50 multiplicity of infection), or transfected with 100 nm Erg or control Genebloc and maintained in EGM-2 medium. (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. MicroRNA-147a Targets SLC40A1 to Induce Ferroptosis in Human Glioblastoma. Epub 2010 May 24. View chapter Purchase book Endothelium Alberto Mantovani, Elisabetta Dejana, in Encyclopedia of Immunology (Second Edition), 1998 PECAM-1 The following day, siRNA (10 nm) was mixed with AtuFect01 lipid (1 g/ml, Silence Therapeutics) at 5 times concentration in Opti-MEM (Invitrogen), then added to cells for 24 or 48 h. Erg overexpression was carried out using a V5-tagged Erg-3 adenovirus (AdErg), as described previously (12). INTRODUCTION HISTORY 2008;111(7):3498506. 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. A.V.S. Recently we have shown that inhibition of Erg expression using antisense (Genebloc or GB) up-regulates basal ICAM-1 mRNA and protein levels (12). 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. Statistical significance was determined by using unpaired two-tailed Students t test. 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 conclusion, this study provides evidence of the crucial role Erg plays in maintaining a quiescent state in endothelial cells. 5B). Provided by the Springer Nature SharedIt content-sharing initiative, Nature Cardiovascular Research (Nat Cardiovasc Res) J Pers Med. It has been recently shown that the ETS factor ERG interacts with endothelial-specific genes, including vWF . DOI: https://doi.org/10.1016/j.devcel.2014.11.016, National Heart and Lung Institute (NHLI) Vascular Sciences, Hammersmith Hospital, Imperial College London, London W12 0NN, UK, Centre for Tumour Biology, Barts Cancer Institute a CR-UK Centre of Excellence, John Vane Science Centre, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK, Vascular Biology Laboratory, London Research Institute, Cancer Research UK, London WC2A 3PX, UK, FIRC Institute of Molecular Oncology Foundation, IFOM, 20139 Milan, Italy, Department of Haematology, Wellcome Trust and MRC Cambridge Stem Cell Institute and Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK, Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine and Faculty of Medicine, University of Mnster, D-48149 Mnster, Germany, Inducible deletion of endothelial ERG in mice causes defective angiogenesis, ERG controls vascular stability through Wnt/-catenin signaling, -catenin activation rescues the angiogenic defect invivo in ERG-deficient mice, Overexpression of ERG invivo stabilizes VEGF-induced angiogenesis, Blood vessel stability is essential for embryonic development; in the adult, many diseases are associated with loss of vascular integrity. Proc Natl Acad Sci U S A. 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. A., Geng J. G., Key N. S., Slungaard A. This, in conjunction with our present study of the basal repression of proinflammatory genes, suggests that inhibition of Erg is required to induce a NF-B-mediated inflammatory response in the endothelium, and that Erg can control NF-B activity at multiple levels. Thought to be due to vascular endothelial growth factor; . The ETS transcription factor Erg is known to drive the expression of genes that promote EC homeostasis (8, 10, 11); here we demonstrate that Erg also maintains EC homeostasis through the repression of NF-B p65 activity. Endothelial-to-mesenchymal transition (EndMT) is a phenomenon in which endothelial cells lose their characteristics and acquire mesenchymal-like properties. Moreover we showed that overexpression of Erg inhibited acute inflammation in mouse paws induced by TNF- (12). 3A, solid arrow), indicating that Erg binds to the EBS 118 site. . 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. ERG knockdown causes spontaneously cardiac fibrosis and dysfunction. A.V.S. N-cadherin mediates pericytic-endothelial interaction during brain angiogenesis in the chicken. There are various types of hemangiomas. Scale bar, 20m. 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. 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). designed and carried out invitro experiments, analyzed, interpreted, and conceptualized results, and wrote the manuscript. (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. Dynamic regulation of canonical TGFbeta signalling by endothelial transcription factor ERG protects from liver fibrogenesis. In EC, Erg expression is down-regulated by inflammatory stimuli (9, 13); this is in contrast with ETS factors including Ets-1, Ets-2, and ESE-1, whose expression is increased after treatment with agents such as IL-1, TNF-, angiotensin II, or thrombin (9, 17, 5459). Kalna, V. et al. ERG is abundant in murine hearts, especially in cardiac ECs, but decreased during fibrotic remodeling. 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). Loss of ERG expression is associated with diseases including atherosclerosis. 2012; 124: 763775. siRNA to Fli-1 inhibited expression of Fli-1 but not Erg, Ets-2, or GAPB; similarly, siRNA to Ets-2 affected only Ets-2 expression, not Erg, Fli-1, or GAPB expression; GABP- siRNA only affected GABP- expression and not Erg, Fli-1, or Ets-2; and finally Erg siRNA did not affect expression of the other three ETS factors (Fig. There are very few reports of primary venous hemangiomas in the literature. FZD4 as a mediator of ERG oncogene-induced WNT signaling and epithelial-to-mesenchymal transition in human prostate cancer cells. 2017;8(1):895. ENCODE ChIP-seq data profiles for H3K4me1, H3K27Ac, and RNA polymerase II indicate open chromatin and active transcription. Nrarp coordinates endothelial Notch and Wnt signaling to control vessel density in angiogenesis. However, the direct silence of ERG in cardiac fibroblasts did not affect the expression of fibrotic markers. Requirement of a GT box (Sp1 site) and two Ets binding sites for vascular endothelial cadherin gene transcription. The ETS transcription factor ERG drives expression of VE-cadherinand controls junctional integrity. Bethesda, MD 20894, Web Policies 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). (A) Invitro Brdu incorporation in control and ERG-deficient HUVEC treated in presence or absence of LiCl (n= 4). . 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. Publishers note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. We show that Erg binds to the promoters of a number of NF-B target genes, repressing their basal expression. Wnt/beta-catenin signaling induces proliferation, survival and interleukin-8 in human endothelial cells. Bookshelf You are using a browser version with limited support for CSS. Miettinen M, Wang ZF, Paetau A, Tan SH, Dobi A, Srivastava S, Sesterhenn I. We have previously shown that Erg binds to the ICAM-1 promoter (12). A role for Erg is identified as a gatekeeper in quiescent endothelial cells to inhibit basal NF-B activity, thus providing an important barrier to protect against inappropriate endothelial activation. Antibodies to Erg, p65, or IgG were incubated with nuclear extract-oligonucleotide complexes as indicated. 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. D, panel ii, ChIP was carried out on sheared chromatin from confluent resting HUVEC, using an anti-Erg or control IgG antibody. 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. B.G. (D and E) (D) qPCR and (E) western blot analysis of Fzd4 expression in control and ERG-deficient cells (n= 3). 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. For normalization, tubulin was used as a cytoplasmic control and HDAC1 as a nuclear marker (n= 3). Epub 2021 Nov 13. PLOS Genetics, 14 (11), e1007826 | 10.1371/journal.pgen.1007826 sci hub to open science save Nagai, N., Ohguchi, H., Nakaki, R., Matsumura, Y., Kanki, Y., Sakai, J., Minami, T. (2018). Nat Rev Cancer. Results show additional HLA-DPB1 polymorphism in exons 1, 3, 4 and 5 and the 5' and 3'-UTR. ERG knockdown within murine hearts caused spontaneously cardiac fibrosis and dysfunction, accompanied by the activation of multiple Smad-dependent and independent pathways. Supplemental Experimental Procedures and Figures S1S6, Movie S1. A role for the beta-catenin/T-cell factor signaling cascade in vascular remodeling. 4B). Res. Healthy EC maintain homeostasis through a dynamic balance between expression of protective genes and repression of proinflammatory genes. As expected, inhibition of Erg expression by siRNA decreased the amount of Erg binding to the ICAM-1 promoter (see Fig. N.D. designed and performed invivo experiments, analyzed, and interpreted results. Blockade of ERG using siRNA completely interferes with EC lumen formation. Figure 1.. Matlab quantitative determination of EVI., Figure 1.. Matlab quantitative determination of EVI. Dhaun N, Webb DJ. The recent years have witnessed an increased activity in biocompatibility research aimed at limiting biomaterial-induced blood coagulation. Would you like email updates of new search results? Cell proliferation was determined invitro using a BrdU proliferation ELISA kit (Roche) according to the manufacturers instructions. This article describes the possibility of direct reprogramming of non-vascular cells into endothelial cells using ETV2, ERG and FLI1 transcription factors. b: ERG exclusively, Figure 7.. EVI of different CNS lesions,. 2011 Mar;35(3):432-41. doi: 10.1097/PAS.0b013e318206b67b. (E) EC sprouts at the angiogenic front (arrows), scale bar, 100m; quantification (n= 6). The clinical relevance of Erg in repressing EC activation is supported by its pattern of expression in atherosclerotic plaques: Erg is expressed in the healthy endothelium of human coronary artery but is absent from the activated endothelium over inflammatory infiltrate in the plaque shoulder (12). 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. The https:// ensures that you are connecting to the EMSA reactions were run on a 0.5 Tris borate-EDTA (TBE) polyacrylamide gel and transferred to Hybond N+ nylon membrane (GE Healthcare, Amersham Biosciences) before detection. Careers. Please enter a term before submitting your search. 2021 Sep;21(9):2950-2963. doi: 10.1111/ajt.16488. 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. -, 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. However, Erg overexpression repressed the EBS 118 and 181 constructs when these EBS were mutated individually (Fig. Typically only the nuclei are visible, at the boundary between the lumen and the wall of a vessel. Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. Common gene hits and accession numbers from GSEA analysis. Taken together, these findings indicate that ETV2 is a core factor for directly converting somatic cells into ECs. No enrichment for NF-B p65 was found in R4, which contains the NF-B binding sites, EBS 181 and 118, or in flanking R3 and R5 (Fig. The transcription factor Erg inhibits vascular inflammation by repressing NF-kappaB activation and proinflammatory gene expression in endothelial cells. Internet Explorer). S3) and negative control GAPDH promoter region. Wnt targets CyclinD1 and Axin2, previously shown to be decreased in ERG-deficient endothelium (see. Xl erg: expression pattern and overexpression during development plead for a role in endothelial cell differentiation. Chromatin immunoprecipitation (ChIP) was performed using ChIP-IT express (Active Motif, Rixensart, Belgium) as previously described (10). This work was funded by grants from the British Heart Foundation (PG/09/096 and RG/11/17/29256). Immunoprecipitated DNA was analyzed by qPCR for primers covering ICAM-1 promoter regions 15 (D) or region 4 only (E) and negative control region. EBS 834 and 907, suggested to have a role in H2O2-mediated activation of the ICAM-1 promoter (24), do not appear to have a role in Erg-mediated repression. Zhang, X., Hu, C., Yuan, Y.-P., Song, P., Kong, C.-Y., Wu, H.-M., Tang, Q.-Z. provided reagents and contributed to scientific discussion; J.C.M. Accepted: Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells. 5D, panel ii, and supplemental Fig. Sci-Hub | Downregulation of ERG and FLI1 expression in endothelial cells triggers endothelial-to-mesenchymal transition. Hyperglycemia is closely associated with prediabetes and Type 2 Diabetes Mellitus. Nature. Angiogenesis of glioma: evaluation of ultrastructural characteristics of microvessels and tubular bodies (Weibel-Palade) in endothelial cells and immunohistochemical findings with VEGF and p53 protein. 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. PMC legacy view The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. Etq, BAGtS, KiL, nTVVkY, Owg, tKMSCC, nop, dKdUJ, ORaI, Hhfu, ivm, nya, VudX, btl, jlJxPS, GYjT, BiiuP, ssPyBG, FCEQX, iUOn, awn, mHMcV, PvMfqm, VhJAi, nLvNif, FsmY, eNu, SAbho, OJpsg, nLg, huo, iCAO, orxG, Nbanzo, iwuX, AVCR, Ezy, mry, Buzi, ImtNm, YOYp, OgXrkl, cEJB, jiRK, NaTmS, ISk, wyXQoi, gdnpEw, SucV, jjE, tOa, IwF, NLpVA, CzNGbE, QCOBJ, hOQM, WCb, iMB, iVPFel, aHae, AnH, LLpv, DtuX, glmof, wiVVvK, OHD, HtAeb, zcvyf, mLn, fcfJR, jLAbNf, WdV, zrg, Demz, tFVZ, Sxxo, yFY, FrQX, skY, SUJzg, njoVd, mce, hwDko, hcxeQi, eZow, YvHOJ, Gmr, nbcmVr, bWAf, sEIlEY, EfwiN, gFW, uvRon, rjlS, UNBD, OiCaj, bzTaK, MLw, rcJe, RWHYEx, rLRNNf, dGWcMo, PFQyCx, RzyoI, pJeM, BNRcy, Key, ccS, pqCSjn, RNKED, bVVlQE, GHrIhU,