Transcriptome analysis of inflammation-related gene expression in endothelial cells activated by complement MASP-1
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE98114 | GEO | 2017/09/14
SECONDARY ACCESSION(S): PRJNA384020
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE4919: Translation State Array Analysis of Thrombin Stimulated Human Endothelial Cells GSE5352: Translation State Array Analysis of LPS Stimulated Human Endothelial Cells GSE5353: Translation State Array Analysis of Insulin Stimulated Human Endothelial Cells GSE5354: Translation State Array Analysis of TNF Stimulated Human Endothelial Cells GSE5385: Translation State Array Analysis of Histamine Stimulated Human Endothelial Cells GSE5386: Translation State Array Analysis of Serum Stimulated Human Endothelial Cells Refer to individual Series
2010-07-01 | E-GEOD-5393 | biostudies-arrayexpress
Project description:This model is from the article:
An Integrated Mathematical Model of Thrombin-, Histamine-and VEGF-Mediated Signalling in Endothelial Permeability.
Wei X, Han B, Zhang J, Liu X, Tan C, Jiang Y, Low B, Tidor B, Chen Y. BMC Syst Biol.
2011 Jul 15;5:112. 21756365
,
Abstract:
Endothelial permeability is involved in injury, inflammation, diabetes and cancer. It is partly regulated by the thrombin-, histamine-, and VEGF-mediated myosin-light-chain (MLC) activation pathways. While these pathways have been investigated, questions such as temporal effects and the dynamics of multi-mediator regulation remain to be fully studied. Mathematical modeling of these pathways facilitates such studies. Based on the published ordinary differential equation models of the pathway components, we developed an integrated model of thrombin-, histamine-, and VEGF-mediated MLC activation pathways.
RESULTS:
Our model was validated against experimental data for calcium release and thrombin-, histamine-, and VEGF-mediated MLC activation. The simulated effects of PAR-1, Rho GTPase, ROCK, VEGF and VEGFR2 over-expression on MLC activation, and the collective modulation by thrombin and histamine are consistent with experimental findings. Our model was used to predict enhanced MLC activation by CPI-17 over-expression and by synergistic action of thrombin and VEGF at low mediator levels. These may have impact in endothelial permeability and metastasis in cancer patients with blood coagulation.
CONCLUSION:
Our model was validated against a number of experimental findings and the observed synergistic effects of low concentrations of thrombin and histamine in mediating the activation of MLC. It can be used to predict the effects of altered pathway components, collective actions of multiple mediators and the potential impact to various diseases. Similar to the published models of other pathways, our model can potentially be used to identify important disease genes through sensitivity analysis of signalling components.
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
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To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL1102210000 | BioModels
Project description:We developed a novel substrate-selective inhibitor of p38 MAPK, UM101, and compared its effects on TNF-induced gene expression by human lung microvascular endothelial cells (HMVECLs) with the prototypical p38 catalytic inhibitor, SB203580
2017-01-10 | GSE93330 | GEO
Project description:To investigate the function of histamine signal perceived by HRH1 in the regulation of endothelial angiogenic process, we knocked down HRH1 using shRNA from histamine treated endothelial cells.
2022-08-28 | GSE211726 | GEO
Project description:This model is from the article:
Modelling thrombin generation in human ovarian follicular fluid
Bungay Sharene D., Gentry Patricia A., Gentry Rodney D.
Bulletin of Mathematical BiologyVolume 68, Issue 8, 12 July 2006, Pages 2283-302
16838084,
Abstract:
A mathematical model is constructed to study thrombin production in human ovarian follicular fluid. The model results show that the amount of thrombin that can be produced in ovarian follicular fluid is much lower than that in blood plasma, failing to reach the level required for fibrin formation, and thereby supporting the hypothesis that in follicular fluid thrombin functions to initiate cellular activities via intracellular signalling receptors. It is also concluded that the absence of the amplification pathway to thrombin production in follicular fluid is a major factor in restricting the amount of thrombin that can be produced. Titration of the initial concentrations of the various reactants in the model lead to predictions for the amount of tissue factor and phospholipid that is required to maintain thrombin production in the follicle, as well as to the conclusion that tissue factor pathway inhibitor has little effect on the time that thrombin generation is sustained. Numerical experiments to determine the effect of factor V, which is at a much reduced level in follicular fluid compared to plasma, and thrombomodulin, illustrate the importance for further experimental work to determine values for several parameters that have yet to be reported in the literature.
2011-05-12 | BIOMD0000000332 | BioModels
Project description:This model is from the article:
Modelling thrombin generation in human ovarian follicular fluid
Bungay Sharene D., Gentry Patricia A., Gentry Rodney D.
Bulletin of Mathematical BiologyVolume 68, Issue 8, 12 July 2006, Pages 2283-302
16838084,
Abstract:
A mathematical model is constructed to study thrombin production in human ovarian follicular fluid. The model results show that the amount of thrombin that can be produced in ovarian follicular fluid is much lower than that in blood plasma, failing to reach the level required for fibrin formation, and thereby supporting the hypothesis that in follicular fluid thrombin functions to initiate cellular activities via intracellular signalling receptors. It is also concluded that the absence of the amplification pathway to thrombin production in follicular fluid is a major factor in restricting the amount of thrombin that can be produced. Titration of the initial concentrations of the various reactants in the model lead to predictions for the amount of tissue factor and phospholipid that is required to maintain thrombin production in the follicle, as well as to the conclusion that tissue factor pathway inhibitor has little effect on the time that thrombin generation is sustained. Numerical experiments to determine the effect of factor V, which is at a much reduced level in follicular fluid compared to plasma, and thrombomodulin, illustrate the importance for further experimental work to determine values for several parameters that have yet to be reported in the literature.
2011-05-12 | BIOMD0000000333 | BioModels
Project description:Thrombin exerts pleiotropic effects on the endothelium. Nevertheless, little is known about its capacity to generate endothelial microparticles, a hallmark of endothelial activation. To gain insight into the mechanisms involved in microparticles release, the human microvascular endothelial cell line-1 (HMEC1) was stimulated with thrombin at 1 IU/ml for different times. The gene expression profiling in stimulated HMEC-1 was compared to that obtain with untreated cells.
2006-01-20 | E-MEXP-477 | biostudies-arrayexpress
Project description:Proinflammatory stimuli rapidly and globally remodel chromatin landscape, thereby enabling transcriptional responses. Yet, the mechanisms coupling chromatin regulators to the master regulatory inflammatory transcription factor NF-kB remain poorly understood. We report in human endothelial cells (ECs) that activated NF-kB binds to enhancers, provoking a rapid, global redistribution of BRD4 preferentially at super-enhancers, large enhancer domains highly bound by chromatin regulators. Newly established NF-kB super-enhancers drive nearby canonical inflammatory response genes. In both ECs and macrophages BET bromodomain inhibition prevents super-enhancer formation downstream of NF-kB activation, abrogating proinflammatory transcription. In TNFa-activated endothelium this culminates in functional suppression of leukocyte rolling, adhesion and transmigration. Sustained BET bromodomain inhibitor treatment of LDLr -/- animals suppresses atherogenesis, a disease process rooted in pathological vascular inflammation involving endothelium and macrophages. These data establish BET-bromodomains as key effectors of inflammatory response through their role in the dynamic, global reorganization of super-enhancers during NF-kB activation. Gene expression analysis of human endothelial cells in resting state, treatment with TNFalpha or TNFalpha with the BET bromodomain inhibitor JQ1
2014-09-29 | E-GEOD-53999 | biostudies-arrayexpress
Project description:Gene expression affected by TNFa was investigated, then, p38 inhibitor SB203580 was used to investigate p38 signal pathway. Experiment Overall Design: Fibroblast-like synoviocyte culture was treated with TNFa in the presence and absence of SB203580 and compared to the gene expression not treated with TNFa.
2008-06-15 | E-GEOD-7826 | biostudies-arrayexpress
Project description:The lymphatic vasculature regulates lung homeostasis through drainage of fluid and trafficking of immune cells and plays a key role in the response to lung injury in several disease states. We have previously shown that lymphatic dysfunction occurs early in the pathogenesis of chronic obstructive pulmonary disease (COPD) caused by cigarette smoke (CS) and that this is associated with increased thrombin and fibrin clots in lung lymph. However, the direct effects of CS and thrombin on lymphatic endothelial cells (LECs) in COPD are not entirely clear. Studies of the blood vasculature have shown that COPD is associated with increased thrombin, which causes endothelial dysfunction after CS exposure and is characterized by changes in the expression of coagulation factors and leukocyte adhesion proteins. Here, we determined whether similar changes occur in LECs. We used an in vitro cell culture system and treated human lung microvascular lymphatic endothelial cells with cigarette smoke extract (CSE) and/or thrombin. We found that CSE treatment led to decreased fibrinolytic activity in LECs, which was associated with increased expression of plasminogen activator inhibitor 1 (PAI-1). LECs treated with both CSE and thrombin together had a decreased expression of TFPI and an increased expression of vascular adhesion molecules. RNA sequencing of lung LECs isolated from mice exposed to CS also showed upregulation of prothrombotic and inflammatory pathways at both acute and chronic exposure time points. Analysis of publicly available single-cell RNA sequencing of LECs as well as immunohistochemical staining of lung tissue from COPD patients supported these data and showed an increased expression of inflammatory markers in LECs from COPD patients compared to those from controls. These studies suggest that in parallel with blood vessels, the lymphatic endothelium undergoes inflammatory changes associated with CS exposure and increased thrombin in COPD. Further research is needed to unravel the mechanisms by which these changes affect lymphatic function and drive tissue injury in COPD.
2024-02-12 | GSE255250 | GEO