E-GEOD-52778
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA229998
PROVIDER: E-GEOD-52778 | ExpressionAtlas | 2016-01-08
REPOSITORIES: ExpressionAtlas
Similar Datasets
Project description:Human Airway Smooth Muscle Transcriptome Changes in Response to Asthma Medications
| PRJNA229998 | ENA
Project description:Persistent severe asthma is associated with hyper-contractile airways and structural changes in the airway wall, including an increased airway smooth muscle (ASM) mass. This study used gene expression profiles from asthmatic and healthy airway smooth muscle cells grown in culture to identify novel receptors and pathways that potentially contributed to asthma pathogenesis. We used microarrays to compare the gene expression between asthmatic and healthy airway smooth muscle cells to understand the underlying pathway contributing the differences in cellular phenotypes Asthmatic airway smooth muscle cells (ASMC) are intrinsically different and have a differential transcriptional response to pro-fibrotic, pro-proliferation and pro-inflammatory stimuli than ASMC from healthy patients. We sought to identify genes that are differentially expressed between asthmatic and healthy ASMC under various stimulations which mimic the asthmatic airways. To this end, we obtained human ASMC from bronchial biopsies and explanted lungs from doctor diagnosed asthmatic patients (n=3) and healthy controls (n=3). The ASMC were then grown in culture and treated with pro-fibrotic (Transforming growth factor beta (TGFβ)), pro-proliferation (Fetal Bovine Serum (FBS)) and pro-inflammatory stimuli (Interleukin-1 beta (IL-1β)) for 8 hours. Gene expression was then evaluated using Affymetrix Human Gene 1.0ST arrays.
2015-01-31 | E-GEOD-63383 | biostudies-arrayexpress
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:Persistent severe asthma is associated with hyper-contractile airways and structural changes in the airway wall, including an increased airway smooth muscle (ASM) mass. This study used gene expression profiles from asthmatic and healthy airway smooth muscle cells grown in culture to identify novel receptors and pathways that potentially contributed to asthma pathogenesis. We used microarrays to compare the gene expression between asthmatic and healthy airway smooth muscle cells to understand the underlying pathway contributing the differences in cellular phenotypes
2015-01-31 | GSE63383 | GEO
Project description:Rationale: Asthma is a chronic inflammatory airway disease. The most common medications used for its treatment are β2-agonists and glucocorticosteroids, and one of the primary tissues that these drugs target in the treatment of asthma is the airway smooth muscle. We used RNA-Seq to characterize the human airway smooth muscle (HASM) transcriptome at baseline and under three asthma treatment conditions. Methods: The Illumina TruSeq assay was used to prepare 75bp paired-end libraries for HASM cells from four white male donors under four treatment conditions: 1) no treatment; 2) treatment with a β2-agonist (i.e. Albuterol, 1μM for 18h); 3) treatment with a glucocorticosteroid (i.e. Dexamethasone (Dex), 1μM for 18h); 4) simultaneous treatment with a β2-agonist and glucocorticoid, and the libraries were sequenced with an Illumina Hi-Seq 2000 instrument. The Tuxedo Suite Tools were used to align reads to the hg19 reference genome, assemble transcripts, and perform differential expression analysis using the protocol described in https://github.com/blancahimes/taffeta mRNA profiles obtained via RNA-Seq for four primary human airway smooth muscle cell lines that were treated with dexamethasone, albuterol, dexamethasone+albuterol or were left untreated.
2014-01-01 | E-GEOD-52778 | biostudies-arrayexpress
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:To identify transcriptional differences / intrinsic abnormalities of human airway smooth muscle cells from patients with and without asthma.
2018-10-27 | E-MTAB-7346 | biostudies-arrayexpress
Project description:Asthma is a chronic inflammatory respiratory disease affecting over 300 million people around the world. Some asthma patients remain poorly controlled by conventional therapies and experience more life-threatening exacerbations. While patients with severe, refractory disease represent a heterogeneous group, a feature shared by most includes glucocorticoid insensitivity. We sought to characterize differences in the airway smooth muscle transcriptome response to glucocorticoids in fatal asthma vs. non-asthma donors. RNA-Seq was used to measure airway smooth muscle transcript expression differences between 9 donors with fatal asthma and 8 non-asthma donors. Cells from each donor were treated with budesonide or with vehicle control. Poly(A)-selected RNA-Seq libraries were prepared with the Illumina TruSeq method. An Illumina HiSeq 2500 instrument was used to generate 125 base pair paired-end reads.
2018-12-31 | GSE94335 | GEO
Project description:Asthma is a very frequent airway disease that affects 6 to 20% of the population. Severe asthma, represents 3 to 5% of all asthmatic patients and is histologically characterized by an increased bronchial smooth muscle (BSM) mass and clinically by viral exacerbations. Functionally, BSM remodeling had a poor prognostic value in asthma, since higher BSM mass was associated with lower lung function and increased exacerbation rate. However, the role of BSM as a potential actor of asthma exacerbation has only been sparsely suggested. We thus hypothesis that asthmatic BSM cells could act on bronchial epithelium and modified its response to rhinovirus infection.
2023-05-02 | PXD015604 | Pride
Project description:Rationale: Asthma and atopy shares common features including Th2-inflammation. However, impairment of airway function seems to be absent in atopy. Increased understanding of the complex cellular and molecular pathways defining the similarities and differences between asthma and atopy may be achieved by transcriptomic analysis (RNA-Seq). Hypothesis and Aims: As the airway smooth muscle (ASM) layer plays an important role in airway function, we hypothesized that the transcriptomic profile of the ASM layer in endobronchial biopsies is different between atopic asthma patients and atopic healthy controls. First, we examined the differences in transcriptomic profiles of the ASM layer in endobronchial biopsies between atopic mild, steroid-free asthma patients, and atopic and non-atopic healthy controls. Second, we investigated the association between the transcriptomic profiles of the ASM layer and airway function. Methods: This cross-sectional study included 12 steroid-free atopic asthma patients, 6 atopic, and 6 non-atopic healthy controls. RNA of ASM from 4 endobronchial biopsies per subject was isolated and sequenced (GS FLX+, 454/Roche). Ingenuity Pathway Analysis was used to identify gene networks. Comparison of the numbers of reads per gene in asthma and controls was based on the negative binomial distribution. At the current sample size the estimated false discovery rate was approximately 1%. Results: Yield of isolated RNA was 30-821ng. We identified 174 differentially expressed genes between asthma and atopic controls, 108 between asthma and non-atopic controls, and 135 between atopic and non-atopic controls. A set of 8 genes was identified, which seems to define asthma patients from non-asthmatic controls regardless of atopy. Four of these genes were significantly associated with airway hyperresponsiveness. Conclusion: A difference in transcriptomic profile of the airway smooth muscle layer in asthma patients compared to atopic and non-atopic healthy controls may lead to a different regulation of inflammatory pathways and of airway smooth muscle function and development resulting in impaired airway function. This cross-sectional transcriptomics study consisted of 2 visits. At visit 1, asthma patients (n=12), and healthy atopic (n=6) and non-atopic (n=6) controls were screened for eligibility to participate according to the in- and exclusion criteria. Spirometry and a methacholine bronchoprovocation test were performed. At visit 2, FEV1 reversibility was measured and 4 endobronchial biopsies per subject were collected during a bronchoscopy. Airway smooth muscle was collected from the biopsies by laser capture microdissection and total RNA isolated. cDNA was prepared using the Ovation RNA-Seq System (NuGEN). RNA-Seq was performed using the GS FLX+ instrument (454/Roche). Sequence reads were mapped against the human genome (hg19; UCSC). Comparison of the numbers of reads per gene between asthma and healthy controls was based on the negative binomial distribution and carried out with the R package DESeq including correction for multiple testing.
2014-08-15 | E-GEOD-38003 | biostudies-arrayexpress