Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA290481 | ENA |
REPOSITORIES: ENA
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Project description:High uniform fluid shear stress (FSS) is atheroprotective and preserves the endothelial phenotype and function through activation of downstream mediators such as MAPK7 (Erk5). Endothelial cells respond to FSS thanks to mechanotransduction. However, how the resulting signaling is integrated and resolved at the epigenetic level, remains elusive. We hypothesized that Polycomb methyltransferase EZH2 is involved in the effects of FSS in human endothelial cells. We showed that FSS decreases the expression of the Polycomb methyltransferase EZH2. Despite simultaneous activation of MAPK7, MAPK7 pathway does not directly influence the transcription of EZH2. Interestingly though, the knock down of EZH2 activates the protective MAPK7 signaling in endothelial cells, even in the absence of FSS. To understand the influence of the FSS-decreased expression of EZH2 on endothelial transcriptome, we performed RNA-seq and differential gene expression analysis. We identified candidate groups of genes dependent on both EZH2 and FSS. Among those, Gene Ontology overrepresentation analysis revealed highly significant enrichment of the cell cycle-related genes, suggesting changes in proliferation. Indeed, the depletion of EZH2 strongly inhibited endothelial proliferation, indicating cell cycle arrest. The concomitant decrease in CCNA expression suggests the transition of endothelial cells into a quiescent phenotype. Further bioinformatical analysis suggested TXNIP as a possible mediator between EZH2 and cell cycle-related gene network. Our data show that EZH2 is a FSS-responsive gene. Decreased EZH2 levels enhance the activation of the atheroprotective MAPK7 signaling. Decrease in EZH2 under FSS mediates the decrease in the expression of the network of cell cycle-related genes, which allows the cells to enter quiescence. EZH2 is therefore important for the protective effects of FSS in endothelium.
2015-09-25 | GSE71164 | GEO
Project description:The effect of hemodynamic shear stress on endothelial gene expression was investigated in the porcine iliac arteries. Computational fluid dynamics simulations identified three anatomical regions likely to experience high, medium, and low shear stress. The expression of genes in endothelial cells recovered from these regions were assessed using microarray. Keywords: shear stress, endothelial cell gene expression, in vivo
2009-03-31 | GSE10671 | GEO
Project description:The effect of hemodynamic shear stress on endothelial gene expression was investigated in the porcine iliac arteries. Computational fluid dynamics simulations identified three anatomical regions likely to experience high, medium, and low shear stress. The expression of genes in endothelial cells recovered from these regions were assessed using microarray. Keywords: shear stress, endothelial cell gene expression, in vivo 11 iliac arteries were obtained from 6 animals, total RNA were extracted from high, medium and low shear region. The expression profiles were compared with a reference RNA using dual channel arrays. Samples with low original RNA quality and low hybridization quality were not included.
2009-03-31 | E-GEOD-10671 | biostudies-arrayexpress
Project description:Fluid induced shear stress is widely recognized as an important biophysical signal in cell-cell mechanotransduction. To identify cellular signaling pathways that are regulated by fluid shear stress, we applied the unbiased approach of transcriptional profiling. Our cDNA array analysis detected that 1165 of the 6288 sampled unigenes were significantly affected by pulsatile fluid flow. GenMapp 2.1 analysis revealed pathways of genes regulated by shear stress: angiogenesis, blood vessel morphogenesis, regulation of endothelial cell proliferation and prostaglandin biosynthesis. Individual genes significantly up-/down-regulated by shear stress included vascular endothelial growth factor A (VEGFa), cysteine rich protein 61 (CRY61), platelet derived growth factor, alpha (PDGFa), connective tissue growth factor (CTGF), Neuropilin 1 (NRP1), angiotensin II receptor, type 1a (AGTR1a) and fibroblast growth factor 1 (FGF1). Based on these findings, we hypothesize that fluid shear stress regulated VEGF most likely stimulates MC3T3-E1 cells through autocrine/paracrine release and may provide a powerful recruitment signal for osteoclasts, endothelial cells and/or stem cells during bone remodeling. Keywords: stress response
2007-06-20 | GSE8117 | GEO
Project description:In order to simulate the effects of shear stress in regions of the vasculature prone to developing atherosclerosis, we subjected human umbilical vein endothelial cells to reversing shear stress, in order to mimic hemodynamic conditions at the wall of the carotid sinus, a site of complex, reversing blood flow and commonly observed atherosclerosis. We compared the effects of reversing shear stress (time-average 1 dyne/cm2, maximum +11 dynes/cm2, minimum -11 dynes/cm2, 1 Hz), arterial steady shear stress (15 dynes/cm2), and low steady shear stress (1 dyne/cm2) in terms of gene expression, cell proliferation, and monocyte adhesiveness. Microarray analysis revealed most differentially expressed genes were similarly regulated by all three shear stress regimens when compared to static culture. Comparisons of the three shear stress regimens to each other allowed identification of 138 genes regulated by low average shear stress and 22 by fluid reversal. Functional assays indicated that low average shear stress induces increased cell proliferation as compared to high shear stress. Reversing shear stress was the only condition that induced monocyte adhesion. Monocyte adhesion was partially inhibited by incubation of the endothelial cells with ICAM-1 blocking antibody. Increased surface heparin sulfate proteoglycan expression was observed in cells exposed to reversing shear stress. When these cells were treated with heparinase III monocyte adhesion was significantly reduced. Our results suggest that low steady shear stress is the major impetus for differential gene expression and cell proliferation, while reversing flow regulates monocyte adhesion.
2009-11-16 | GSE16706 | GEO
Project description:Vasculature permeate our entire body and involved in homeostasis and progression of various disease. Endothelium is a backbone of cardiovascular system and endothelial disfunction is associated with most forms of cardiovascular disease from atherosclerosis to chronic heart failure. Decrease in shear stress, particularly due to disturbance of the blood flow by bends or vascular obstruction, lead to atherosclerosis and endothelial disfunction. Notch signaling may act as mechanosensor and assumed to be one of the central signal pathways associated with endothelial disfunction. Association of shear stress, Notch and endothelial dysfunction is well known, molecular mechanisms connected these factors still poorly understood. One might assume that long-term shear stress and dysregulation of Notch in endothelium cause changes in epigenomic profile. While epigenomic changes in shear stressed environment are known to be involved in endothelial disfunction, possible connection of Notch and epigenetic changes in endothelium has not yet been tested. Therefore, here we analyzed how activation of Notch signaling influence on histone code and secretome of endothelial cells in vitro. We found that activation of Notch increase level of N-acetylated forms of Histone 1: H1-0, H1-3, H1-4, H1-5, H1-10. These changes were also associated with changes in secretome profile of endothelium and might have broad biomedical significance in case of endothelial dysfunction.
2023-02-15 | PXD032978 | Pride
Project description:The lymphatic system removes fluid from the interstitial space and returns it to the blood with a tremendous capacity: during inflammation, lymph flow rates can increase dramatically; however, during chronic lymphedema, there is little or no flow. The ability of lymphatic endothelium to sense and actively regulate this function is unknown, and shear stress is likely a key indicator of lymph flow. We profiled gene expression in human dermal microvascular lymphatic endothelial cells exposed to 0, 2 and 20 dyn/cm2 shear stress as representative of chronic lymphedema, normal, and acute inflammatory conditions, respectively. We found important adaptive responses correlated to multiple aspects of lymphatic function. Importantly, shear stress upregulated intracellular water and solute transporters while decreasing cell-cell adhesion and basement membrane components and increasing cell-matrix interactions. This data indicate that during high loading conditions, both passive and active drainage function increases, while conversely when fluid drainage is blocked, transport function is diminished in the lymphatic endothelium. These data demonstrate the first functional-adaptive response of lymphatic endothelium to flow conditions, thus indicating that the lymphatic endothelium plays an active role in regulating their function. Keywords: Shear stress, dose response, cell type comparison Lymphatic endothelial cells were subjected to 0, 2, or 20 dyn/cm2 shear stress; blood endothelial cells were subjected to 0 or 20 dyn/cm2 shear stress. Four samples were used for each cell type/shear level group for a total of 20 samples. Each sample was independently compared to human universal reference RNA via two-color microarray analysis for a total of 20 arrays. In all cases, the experimental samples were labeled with Cy5 dye while the reference RNA was labeled with Cy3.
2009-11-30 | E-GEOD-8852 | biostudies-arrayexpress
Project description:The role of shear stress, the frictional force of blood flow, on the endothelium has been well documented. Differences in shear stress can have profound effects on endothelial and blood vessel biology. Endothelial cells (ECs), termed endocardial ECs, line the heart chambers and are exposed to complex shear stress patterns. While it has been demonstrated that shear stress is important for heart development, little has been shown on the role of shear stress on adult ECs. 4D-MRI studies demonstrate regional differences in blood residence time. We sought to determine the effect of regional differences in endocardial shear stress on the endocardial transcriptome using RNA sequencing (RNA-seq) on 3 different regions (apex, mid-ventricle, outflow tract) from 8 adult pigs, for a total of 24 RNA-seq assays.
2015-12-31 | E-MTAB-3669 | biostudies-arrayexpress
Project description:Schistosomiasis is a chronic and debilitating disease caused by a trematode of the genus Schistosoma. The current strategy for the control of the disease involves treatment with Praziquantel, the only available drug. The development of new drugs is therefore a top priority. Drugs that inhibit histone modifying enzymes have been used in cancer, altering gene expression, replication, repair and DNA recombination. Schistosoma parasites have some characteristics similar to malignant tumors, such as intense cell division and high levels of metabolic activity. Here we evaluate in Schistosoma mansoni the effect of GSK343, an inhibitor of the histone methyltransferase EZH2 that had been shown to arrest or reduce the growth of human cancer cells. We show that GSK343 causes damage to the parasite tegument and reduces egg laying in vitro, concomitant with a decrease in levels of H3K27me3, the histone mark put in place by EZH2. RNA-seq and proteomic analyses of treated parasites showed changes in the expression of hundreds of genes involved in important metabolic processes. In females, a marked decrease was observed in the expression of genes related to processes such as DNA replication and noncoding RNA metabolism. In conclusion, the histone methyltransferase EZH2 seems to be a promising novel drug target against schistosomiasis.
2018-11-23 | PXD010342 | Pride
Project description:Renal epithelial cells are exposed to mechanical forces due to flow-induced shear stress within the nephrons. We applied RNA sequencing to get a comprehensive overview of fluid-shear regulated genes and pathways in the immortalized renal proximal tubular epithelial cell line. Cells were exposed to laminar fluid shear stress (1.9 dyn/cm2) in a cone-plate device and compared to static controls.
2018-03-15 | E-MTAB-6640 | biostudies-arrayexpress