ONTOLOGY SOURCE REFERENCE
Term Source Name	"mo"	"The MGED Ontology"	"ArrayExpress"	""	"NCI_thesaurus"	"EFO"	"NCBITaxon"	"MSH"	"BTO"	"UO"	"CHEBI"	"XCO"	
Term Source File	"http://mged.sourceforge.net/ontologies/MGEDontology.php"	"http://www.ebi.ac.uk/arrayexpress"	""	"ncithesaurus.obo.alt"	"http://www.ebi.ac.uk/efo/"	""	"http://bioportal.bioontology.org/ontologies/47845"	"http://bioportal.bioontology.org/ontologies/46836"	"http://bioportal.bioontology.org/ontologies/50688"	"http://www.ebi.ac.uk/ontology-lookup/browse.do?ontName=UO"	"http://bioportal.bioontology.org/ontologies/50716"	"http://bioportal.bioontology.org/ontologies/50737"	
Term Source Version	""	""	""	""	""	""	"47845"	"46836"	"50688"	"Jun 2010"	"50716"	"50737"	
Term Source Description	""	""	""	""	""	""	"National Center for Biotechnology Information (NCBI) Organismal Classification"	"Medical Subject Headings"	"BRENDA Tissue and Enzyme Source Ontology"	"Unit Ontology"	"Chemical Entities of Biological Interest Ontology"	"Experimental Conditions Ontology"	
INVESTIGATION
Investigation Identifier	""
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Comment [Last Opened With Configuration]	""
INVESTIGATION PUBLICATIONS
Investigation PubMed ID	""
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INVESTIGATION CONTACTS
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STUDY
Study Identifier	"E-GEOD-3589"
Study Title	"Transcription profiling of human umbilical vein endothelial cells (HUVEC) treated with thrombin and leukotriene D4 (LTD4) with ethanol controls to delineate"
Study Description	"Cysteinyl leukotrienes (cysLT), i.e. LTC4, LTD4, and LTE4, are lipid mediators derived from the 5-lipoxygenase pathway. The cysLT receptors cysLT1-R and cysLT2-R are expressed on different target cells and mediate inflammatory reactions in tissue- and LT-R-specific ways. Though endothelial cells (ECs) predominantly express cysLT2-Rs, their role in vascular biology remains to be defined. To delineate cysLT2-R's action, we stimulated human umbilical vein EC with 100 nM LTD4 for 60 min, determined gene signatures by microarrays, and characterized the resulting EC phenotypes. As controls, we compared LTD4-induced genes with those induced by 10 nM thrombin, a prototype vasoactive activator of EC that binds to protease-activated receptor 1 (PAR-1). Following application of stringent filters 37 LTD4-upregulated genes were identified (> 2.5fold stimulation). Surprisingly, most of the LTD4-regulated genes were also induced by thrombin and expression of cysLT2-R- and PAR-1-regulated genes strongly correlated (Pearson correlation coefficient: r = 0.90). Moreover, LTD4 + thrombin, when added together, augmented expression of LTD4- or thrombin-stimulated genes (Wilcoxon signed rank test: p < 0.01). Prominently induced genes that may play roles in vascular injury were studied in detail: Early growth response (EGR) and nuclear receptor subfamily 4 group A; E-selectin; CXC ligand 2; interleukin 8 (IL-8); a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif 1 (ADAMTS-1); and tissue factor (TF). Transcripts of these genes peaked at approximately 60 min, were unaffected by the cysLT1-R antagonist montelukast, and were superinduced by cycloheximide. The EC phenotype was markedly altered: LTD4 induced de novo synthesis of EGR1 protein and EGR1 localized in the nucleus in LTD4-stimulated cells; LTD4 upregulated IL-8 formation and secretion; and LTD4 raised TF protein and TF-dependent EC pro-coagulant activity. These data show that cysLT2-R activation results in a pro-inflammatory EC phenotype through activation of immediate-early genes that resemble those induced by PAR-1. As LTD4 and thrombin are formed concomitantly during vascular injury and pro-thrombotic states, cysLT2-R and PAR-1 may collaborate in vivo to mediate vascular injury and repair. Experiment Overall Design: HUVEC in passage 1 were cultured in serum-free EC medium until cells reached confluency. HUVEC were stimulated by 100 nM LTD4 (n = 4) or 10 nM thrombin (n = 4) or both agonists concomitantly (n = 3). The immediate-early gene programs of these experimental groups were identified at 60 minutes. In addition, one HUVEC preparation was stimulated with 100 nM LTD4 for 6 h and 24 h."
Comment[Study Grant Number]	""
Comment[Study Funding Agency]	""
Study Submission Date	""
Study Public Release Date	"2007-10-27"
Study File Name	"s_E-GEOD-3589_study_samples.txt"
STUDY DESIGN DESCRIPTORS
Study Design Type	"time_series_design"	"compound_treatment_design"	"co-expression_design"	"transcription profiling by array"
Study Design Type Term Accession Number	""	""	""	""
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STUDY PUBLICATIONS
Study PubMed ID	"16606835"
Study Publication DOI	"16606835"
Study Publication Author List	"Barbara Uzonyi, Katharina Lötzer, Steffen Jahn, Cornelia Kramer, Markus Hildner, Ellen Bretschneider, Dörte Radke, Michael Beer, Rüdiger Vollandt, Jilly F Evans, Colin D Funk, Andreas J R Habenicht"
Study Publication Title	"Cysteinyl leukotriene 2 receptor and protease-activated receptor 1 activate strongly correlated early genes in human endothelial cells."
Study Publication Status	"journal_article"
Study Publication Status Term Accession Number	""
Study Publication Status Term Source REF	"The MGED Ontology"
STUDY FACTORS
Study Factor Name	"time"	"dose"	"compound"
Study Factor Type	"time"	"dose"	"compound"
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STUDY ASSAYS
Study Assay File Name	"a_E-GEOD-3589_GeneChip_assay.txt"
Study Assay Measurement Type	"transcription profiling"
Study Assay Measurement Type Term Accession Number	""
Study Assay Measurement Type Term Source REF	""
Study Assay Technology Type	"DNA microarray"
Study Assay Technology Type Term Accession Number	""
Study Assay Technology Type Term Source REF	""
Study Assay Technology Platform	""
STUDY PROTOCOLS
Study Protocol Name	"P-GEOD-3589-7"	"P-GEOD-3589-18"	"P-GEOD-3589-12"	"P-GEOD-3589-5"	"P-GEOD-3589-14"	"P-GEOD-3589-2"	"P-GEOD-3589-3"	"P-GEOD-3589-11"	"P-GEOD-3589-9"	"P-GEOD-3589-6"	"P-GEOD-3589-19"	"P-GEOD-3589-20"	"P-GEOD-3589-13"	"P-GEOD-3589-21"	"P-GEOD-3589-1"	"P-GEOD-3589-16"	"P-GEOD-3589-8"	"P-GEOD-3589-4"	"P-GEOD-3589-15"	"P-GEOD-3589-10"	"P-GEOD-3589-17"
Study Protocol Type	"specified_biomaterial_action"	"specified_biomaterial_action"	"specified_biomaterial_action"	"specified_biomaterial_action"	"specified_biomaterial_action"	"specified_biomaterial_action"	"specified_biomaterial_action"	"specified_biomaterial_action"	"specified_biomaterial_action"	"specified_biomaterial_action"	"specified_biomaterial_action"	"specified_biomaterial_action"	"specified_biomaterial_action"	"specified_biomaterial_action"	"specified_biomaterial_action"	"specified_biomaterial_action"	"specified_biomaterial_action"	"specified_biomaterial_action"	"specified_biomaterial_action"	"specified_biomaterial_action"	"specified_biomaterial_action"
Study Protocol Type Term Accession Number	""	""	""	""	""	""	""	""	""	""	""	""	""	""	""	""	""	""	""	""	""
Study Protocol Type Term Source REF	""	""	""	""	""	""	""	""	""	""	""	""	""	""	""	""	""	""	""	""	""
Study Protocol Description	"Cells stimulated for 1 hour with 100 nM LTD4 + 10 nM thrombin"	"Cells stimulated for 24 hours with 0.05% ethanol"	"Cells stimulated for 1 hour with 0.05% ethanol"	"Cells stimulated for 1 hour with 10 nM thrombin + 0.05% ethanol"	"Cells stimulated for 1 hour with 10 nM thrombin + 0.05% ethanol"	"Cells stimulated for 1 hour with 100 nM LTD4"	"Cells stimulated for 1 hour with 0.05% ethanol"	"Cells stimulated for 1 hour with 100 nM LTD4 + 10 nM thrombin"	"Cells stimulated for 1 hour with 100 nM LTD4"	"Cells stimulated for 1 hour with 10 nM thrombin + 0.05% ethanol"	"Cells stimulated for 24 hours with 100 nM LTD4"	"Cells stimulated for 24 hours with 10 nM thrombin + 0.05% ethanol"	"Cells stimulated for 1 hour with 100 nM LTD4"	"Cells stimulated for 6 hours with 10 nM thrombin + 0.05% ethanol"	"Cells stimulated for 1 hour with 0.05% ethanol"	"Cells stimulated for 6 hours with 0.05% ethanol"	"Cells stimulated for 1 hour with 0.05% ethanol"	"Cells stimulated for 1 hour with 100 nM LTD4"	"Cells stimulated for 1 hour with 100 nM LTD4 + 10 nM thrombin"	"Cells stimulated for 1 hour with 10 nM thrombin + 0.05% ethanol"	"Cells stimulated for 6 hours with 100 nM LTD4"
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STUDY CONTACTS
Study Person Last Name	"Habenicht"
Study Person First Name	"Andreas Johann Richard"
Study Person Mid Initials	""
Study Person Email	"andreas.habenicht@mti.uni-jena.de"
Study Person Phone	""
Study Person Fax	""
Study Person Address	"Institute Vascular Medicine, Medicine, Vascular Medicine, Bachstr. 18, Jena, 07743, Germany"
Study Person Affiliation	"Vascular Medicine"
Study Person Roles	"submitter"
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