Genome-wide gene methylation study in primary cultured airway smooth muscle cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE146376 | GEO | 2020/03/30
REPOSITORIES: GEO
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Project description:We generated genome-wide expression data from primary cultured airway smooth muscle cells (ASMCs) exposed to IL-13, IL-17, IL-13+IL-17, and vehicle. This data was generated in combination with genome-wide methylation data from the same individuals.
2020-03-30 | GSE146374 | GEO
Project description:Selective stimulation of IL-4 receptor on smooth muscle induces airway hyper-responsiveness in mice. Abstract: Production of the cytokines IL-4 and IL-13 is increased in both human asthma and mouse asthma models and Stat6 activation by the common IL-4/IL-13R drives most mouse model pathophysiology, including airway hyperresponsiveness (AHR). However, the precise cellular mechanisms through which IL-4Rα induces AHR remain unclear. Overzealous bronchial smooth muscle constriction is thought to underlie AHR in human asthma, but the smooth muscle contribution to AHR has never been directly assessed. Furthermore, differences in mouse vs. human airway anatomy and observations that selective IL-13 stimulation of Stat6 in airway epithelium induces murine AHR raise questions about the importance of direct IL-4R effects on smooth muscle in murine asthma models and relevance of these models to human asthma. Using transgenic mice in which smooth muscle is the only cell type that expresses or fails to express IL-4Rα, we demonstrate that direct smooth muscle activation by IL-4, IL-13, or allergen is sufficient, but not necessary, to induce AHR and show that 5 genes known to promote smooth muscle migration, proliferation and contractility are activated by IL-13 in smooth muscle in vivo. These observations demonstrate that IL-4Rα promotes AHR through multiple mechanisms and provide a model for testing smooth muscle-directed asthma therapeutics.
2011-01-07 | GSE26476 | GEO
Project description:Selective stimulation of IL-4 receptor on smooth muscle induces airway hyper-responsiveness in mice. Abstract: Production of the cytokines IL-4 and IL-13 is increased in both human asthma and mouse asthma models and Stat6 activation by the common IL-4/IL-13R drives most mouse model pathophysiology, including airway hyperresponsiveness (AHR). However, the precise cellular mechanisms through which IL-4Rα induces AHR remain unclear. Overzealous bronchial smooth muscle constriction is thought to underlie AHR in human asthma, but the smooth muscle contribution to AHR has never been directly assessed. Furthermore, differences in mouse vs. human airway anatomy and observations that selective IL-13 stimulation of Stat6 in airway epithelium induces murine AHR raise questions about the importance of direct IL-4R effects on smooth muscle in murine asthma models and relevance of these models to human asthma. Using transgenic mice in which smooth muscle is the only cell type that expresses or fails to express IL-4Rα, we demonstrate that direct smooth muscle activation by IL-4, IL-13, or allergen is sufficient, but not necessary, to induce AHR and show that 5 genes known to promote smooth muscle migration, proliferation and contractility are activated by IL-13 in smooth muscle in vivo. These observations demonstrate that IL-4Rα promotes AHR through multiple mechanisms and provide a model for testing smooth muscle-directed asthma therapeutics. For the microarray aspect of of the study, there were three groups of mice: 1. IL4R gene knockout (KO) mice 2. WT mice 3. IL4R KO mice that were also transgenic for a gene construct that expressed IL4R under the control of the smooth muscle-specific promoter from the SMP8 gene All mice were subjected to intratracheal IL13 exposure for 7 days, and whole lung RNA was prepared for microarray analysis 24 hours after the last instillation. Per treatment and genotype: Two RNA pools were made from four mice each. These were labeled and hybridized to make a total of 6 microarrays. RNA was labeled with the standard Affymetrix 3' labeling protocol to make cDNA that was hybridized to Mouse MOE 430 plus 2.0 GeneChips. Gene transcripts were identified that differed in their relative expression as a function of IL4R expression on the smooth muscle cells.
2011-01-07 | E-GEOD-26476 | biostudies-arrayexpress
Project description:Interleukin (IL)-17 plays an important and protective role in host defence and has been demonstrated to orchestrate airway inflammation by cooperating with and inducing proinflammatory cytokines. Mircoarrays were used to identify immediate-early/ primary response IL-17A-dependent gene transcripts in primary human bronchial ASM cells from mild asthmatic and healthy individuals. To evaluate IL-17A-inducible gene transcripts, primary human bronchial ASM cells from 3 mild asthmatic and 3 healthy donors were treated for 2h with IL-17 [10ng/ml] and were probed with the Affymetrix GeneChip array. The 2h time point was carefully chosen in order to identify primary response gene targets and to avoid confounding autocrine mechanisms mediating indirect, or late-phase gene expression responses. Non-stimulated ASM cells from the same patients were used as controls.
2012-02-09 | E-GEOD-35643 | biostudies-arrayexpress
Project description:In the short two decades since microRNAs (miRNAs) were discovered, scientists have focused more attention on the biological field of miRNAs. A deeper understanding of the role of miRNAs in development and disease has made miRNAs a powerful tool and target for new therapeutic approaches. However, whether miRNAs are involved in the response of ASMCs to high stretch and high matrix stiffness and their underlying mechanisms remain unclear, especially the relationship between the expression of miRNAs and the biomechanical behavior of ASMCs remains unclear. In this study, we combined bioinformatics and cell mechanics approaches to screen stretch-sensitive and matrix stiffness-sensitive miRNAs and investigate their effects on the biomechanical behaviors of ASMCs.
2023-03-01 | GSE206434 | GEO
Project description:In the short two decades since microRNAs (miRNAs) were discovered, scientists have focused more attention on the biological field of miRNAs. A deeper understanding of the role of miRNAs in development and disease has made miRNAs a powerful tool and target for new therapeutic approaches. However, whether miRNAs are involved in the response of ASMCs to high stretch and high matrix stiffness and their underlying mechanisms remain unclear, especially the relationship between the expression of miRNAs and the biomechanical behavior of ASMCs remains unclear. In this study, we combined bioinformatics and cell mechanics approaches to screen stretch-sensitive and matrix stiffness-sensitive miRNAs and investigate their effects on the biomechanical behaviors of ASMCs.
2023-03-01 | GSE206433 | GEO
Project description:Interleukin (IL)-17 plays an important and protective role in host defence and has been demonstrated to orchestrate airway inflammation by cooperating with and inducing proinflammatory cytokines. Mircoarrays were used to identify immediate-early/ primary response IL-17A-dependent gene transcripts in primary human bronchial ASM cells from mild asthmatic and healthy individuals.
2012-02-09 | GSE35643 | GEO
Project description:Understanding the gene expression changes that are occuring with TGFb1 and IL-13 treatment that result in observed phenotypic changes in bronchial smooth muscle shortening/remodeling.
2023-02-01 | GSE220972 | GEO
Project description:miRNA profiling of mouse kidney arteriolar smooth muscle cells (aSMCs) of the renin lineage comparing control untreated cells with cells treated with forskolin to induce renin expression. Two condition experiment: control untreated aSMCs vs forskolin treated aSMCs; Biological replicates: control 3, treated 3; independently grown and harvested. One replicate per array.
2012-02-25 | E-GEOD-31780 | biostudies-arrayexpress
Project description:Arterial smooth muscle cells (ASMCs) undergo phenotypic changes during development and pathological processes in vivo and during cell culture in vitro. Our previous studies demonstrated that retrovirally-mediated expression of the versican V3 splice variant (V3) that lacks glycosaminoglycan chains by ASMCs retards cell proliferation and migration in vitro and reduces neointimal thickening, macrophage and lipid accumulation in animal models of vascular injury and atherosclerosis. However, the molecular pathways induced by V3 expression that are responsible for these changes are not yet clear. In the present study, we employed a microarray approach to examine how expression of V3 induced changes in gene expression and the molecular pathways in ASMCs. We found that forced expression of V3 by ASMCs affected expression of 521 genes by more than 1.5 fold. Gene ontology (GO) analysis shows that components of extracellular matrix were the most significantly affected by V3 expression, indicating that V3 expression elicits profound remodeling of extracellular matrix. In addition, genes regulating the formation of the cytoskeleton which also serve as markers of contractile smooth muscle cells were significantly upregulated. On the other hand, components of the complement system, chemokines, chemokine receptors, and transcription factors crucial for regulating inflammatory processes were among the genes most downregulated. Consistently, we found that the level of myocardin, a key transcription factor promoting contractile ASMC phenotype, was greatly increased while proinflammatory transcription factors NFkappaB1 and C/EBPβ were significantly attenuated in V3-expressing SMCs. Such results indicate that V3 expression reprograms ASMC into differentiated and anti-inflammatory phenotypes. Overall, these findings demonstrate that expression of V3 reprograms ASMCs promoting anti-inflammatory and differentiated smooth muscle cell phenotypes potentially by altering cell-ECM interaction and focal adhesion signaling pathways. Fischer rat ASMCs were transduced with either a retroviral vector expressing the Versican V3 splice variant (LV3SN) or an empty control vector (LXSN) in three independent experiments. In the first experiment, V3 and control transductions were performed with four technical replicates. In the subsequent two experiments, individual transductions were done for the V3 or control treatments. For data analysis, the technical replicates from the first experiment were averaged, and then data from the three experiments was evaluated in a paired manner.
2015-07-07 | E-GEOD-66624 | biostudies-arrayexpress