MiR-19b mediates lung epithelial-mesenchymal transition via PTEN signaling in response to mechanical stretch
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ABSTRACT:
ORGANISM(S): Mus musculus Rattus norvegicus Homo sapiens
PROVIDER: GSE75100 | GEO | 2015/11/18
SECONDARY ACCESSION(S): PRJNA302441
REPOSITORIES: GEO
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Project description:Acute respiratory distress syndrome (ARDS) is a catastrophic form of acute lung injury (ALI). The necessity for mechanical ventilation (MV) renders patients at risk for ventilator induced lung injury (VILI). Exposure to repetitive cyclic stretch (CS) and/or over-inflation exacerbates injury. Reducing tidal volume (VT) is the only therapeutic strategy shown to mitigate morbidity and mortality. Cyclic stretch has been shown to differentially regulate gene expression in part through the activation of mammalian mitogen-activated protein kinase (MAPK). Although these studies have shown both molecular and cellular alterations, no unifying hypothesis to explain MV-induced lung injury has emerged. In the current study, we hypothesized that coordinated expression of cyclic stretch (CS)-responsive genes relies on the presence of common CS-sensitive regulatory elements. To identify CS-responsive genes, we undertook a comparative examination of the gene expression profile of human bronchial epithelial airway (Beas-2B) cells in response to various injurious stimuli involved in the pathogenesis of acute lung injury (ALI)/Ventilator induced lung injury (VILI): cyclic stretch, tumor necrosis factor alpha (TNF-a), and lipopolysaccharide (LPS). Experiment Overall Design: Human Bronchial Epithelial Cells (Beas-B2) cells grown on silicon elastic plates coated with Type I collagen (Flexercell International, McKeesport, PA) were exposed to six regiments for 4 h: 1) control (static, [control]); 2) mechanical stretch (25 PKa, 30 cycles per min, [stretch]); 3) LPS (1 mcg/ml [LPS]); 4) TNF-α (20 ng/ml; [TNF]); 5) mechanical stretch plus LPS [LPS+S], and 6) mechanical stretch plus TNF-α [TNF+S]. Total RNA (duplicate experiments) was extracted using TRIZOL reagent (as per manufactures specifications) and purified using Qiagen mRNA purification Kit (as per manufacturers specifications). mRNA was hybridized to Affymetrix Human U133plus2.0 chips. Probe based analysis, background reduction, and quantile data normalization was performed in MeV 4.0 of TM4 using Robust Multi-array Average (RMA).
2009-09-15 | E-GEOD-16650 | biostudies-arrayexpress
Project description:Acute respiratory distress syndrome (ARDS) is a catastrophic form of acute lung injury (ALI). The necessity for mechanical ventilation (MV) renders patients at risk for ventilator induced lung injury (VILI). Exposure to repetitive cyclic stretch (CS) and/or over-inflation exacerbates injury. Reducing tidal volume (VT) is the only therapeutic strategy shown to mitigate morbidity and mortality. Cyclic stretch has been shown to differentially regulate gene expression in part through the activation of mammalian mitogen-activated protein kinase (MAPK). Although these studies have shown both molecular and cellular alterations, no unifying hypothesis to explain MV-induced lung injury has emerged. In the current study, we hypothesized that coordinated expression of cyclic stretch (CS)-responsive genes relies on the presence of common CS-sensitive regulatory elements. To identify CS-responsive genes, we undertook a comparative examination of the gene expression profile of human bronchial epithelial airway (Beas-2B) cells in response to various injurious stimuli involved in the pathogenesis of acute lung injury (ALI)/Ventilator induced lung injury (VILI): cyclic stretch, tumor necrosis factor alpha (TNF-a), and lipopolysaccharide (LPS).
2009-08-31 | GSE16650 | GEO
Project description:Cyclic stretch of alveoli is characteristic of mechanical ventilation, and is postulated to be partly responsible for the lung injury and inflammation in ventilator induced lung injury. We propose that miRNAs may regulate some of the stretch response and, therefore, hypothesized that miRNAs would be differentially expressed between stretched and unstretched rat alveolar epithelial cells (RAECs).
2012-03-06 | GSE36256 | GEO
Project description:Cyclic stretch of alveoli is characteristic of mechanical ventilation, and is postulated to be partly responsible for the lung injury and inflammation in ventilator induced lung injury. We propose that miRNAs may regulate some of the stretch response and, therefore, hypothesized that miRNAs would be differentially expressed between stretched and unstretched rat alveolar epithelial cells (RAECs). RAECs were isolated and cultured to express type I epithelial characteristics, after which they were equibiaxially stretched to 25% change in surface area at 15 cycles/minute for 1 or 6 hrs, or served as unstretched controls, and miRNA were extracted (n = 4 for all groups).
2012-03-06 | E-GEOD-36256 | biostudies-arrayexpress
Project description:Myocardial damage caused for example by cardiac ischemia leads to ventricular volume overload resulting in increased stretch of the remaining myocardium. In adult mammals, these changes trigger an adaptive cardiomyocyte hypertrophic response which, if the damage is extensive, will ultimately lead to pathological hypertrophy and heart failure. Conversely, in response to extensive myocardial damage, cardiomyocytes in the adult zebrafish heart and neonatal mice proliferate and completely regenerate the damaged myocardium. We therefore hypothesized that in adult zebrafish, changes in mechanical loading due to myocardial damage may act as a trigger to induce cardiac regeneration. Based, on this notion we sought to identify mechanosensors which could be involved in detecting changes in mechanical loading and triggering regeneration. Here we show using a combination of knockout animals, RNAseq and in vitro assays that the mechanosensitive ion channel Trpc6a is required by cardiomyocytes for successful cardiac regeneration in adult zebrafish. Furthermore, using a cyclic cell stretch assay, we have determined that Trpc6a induces the expression of components of the AP1 transcription complex in response to mechanical stretch. Our data highlights how changes in mechanical forces due to myocardial damage can be detected by mechanosensors which in turn can trigger cardiac regeneration.
2023-12-20 | E-MTAB-13603 | biostudies-arrayexpress
Project description:With gene expression profiling it was aimed to identify the differentially expressed genes associated with the regulation of the cytoskeleton to investigate the stretch-induced cell alignment mechanism. A whole genome microarray based analysis of the stretch-induced gene expression changes was done. Gene expression was measured at the beginning of the alignment process showing first reoriented cells after 5 h stretching and at the end after 24 h, where nearly all cells are aligned. Cyclic mechanical stretching of cells results in cellular alignment perpendicular to the stretch direction regulating cellular response. This stress response is assumed to be an adaptation mechanism to reduce extensive stretching but also acts as architectural restructuring changing performance and biomechanics of the tissue. Gene expression profiling of control vs. stretched primary human dermal fibroblasts after 5 h and 24 h demonstrated the regulation of differentially expressed genes associated with metabolism, differentiation and morphology. Primary human dermal fibroblasts from ten donors were cultured on Bioflex culture plates and stretched for 5h and 24 h or left untreated to avoid changes according to cell culturing. Each of the subject provided 4 samples (control/treated and 5hrs/24hrs) resulting in 40 samples total.
2014-06-11 | E-GEOD-58389 | biostudies-arrayexpress
Project description:With gene expression profiling it was aimed to identify the differentially expressed genes associated with the regulation of the cytoskeleton to investigate the stretch-induced cell alignment mechanism. A whole genome microarray based analysis of the stretch-induced gene expression changes was done. Gene expression was measured at the beginning of the alignment process showing first reoriented cells after 5 h stretching and at the end after 24 h, where nearly all cells are aligned. Cyclic mechanical stretching of cells results in cellular alignment perpendicular to the stretch direction regulating cellular response. This stress response is assumed to be an adaptation mechanism to reduce extensive stretching but also acts as architectural restructuring changing performance and biomechanics of the tissue. Gene expression profiling of control vs. stretched primary human dermal fibroblasts after 5 h and 24 h demonstrated the regulation of differentially expressed genes associated with metabolism, differentiation and morphology.
2014-06-11 | GSE58389 | GEO
Project description:Mechanical stimulation is an important factor for the development of complications after LASIK, but the molecular mechanism still remains unclear. In this study, we have employed whole genome microarray expression profiling as a discovery platform to identify genes responded to mechanical stretch in human corneal keratocytes. Furthermore, the specific signal transduction pathways were discussed. Mechanical stretch regulated gene expression was measured in human corneal keratocytes subjected to cyclic stretch (0-15% elongation, 0.5 Hz, sine waveform) for 0, 1 and 6 hours, respectively. Totally, 840 differentially expressed genes were identified in keratocytes under mechanical stretching, among which 493 genes were up-regulated and 388 genes were down-regulated. Theses differential genes were mainly involved in cytokine-cytokine receptor interaction, ECM-receptor interaction, Focal adhesion, TNF signaling pathway, and MAPK signaling pathway.
2020-12-31 | GSE124138 | GEO
Project description:The retina is often subjected to tractional forces in a variety of conditions, for instance, pathological myopia, proliferative vitreoretinopathy. As the predominant glial element in the sensory retina, Muller cells are responsible for the homeostatic and metabolic support of retinal neurons and active players in virtually all forms of retinal injury and disease. Besides, Muller cells span the entire retinal thickness, extending from the inner to the outer limiting membranes, with cell bodies located in the inner nuclear layer and lateral processes expanding into the plexiform layers of the tissue. Because of this unique morphology, Muller cells can sense even minute changes in the retinal structure because of the mechanical stretching of their long processes or side branches. Thus, itM-bM-^@M-^Ys reasonable to infer that Muller cells also participate in ocular diseases when the retina is overstretched. In this study, we aim to investigate the whole genome regulation of Muller cells under mechanical stretching, which may help in excluding possible molecular mechanisms that would account for many retinal diseases in which the retina is often subjected to mechanical forces. We used microarrays to identify patterns of gene expression changes induced by cyclic mechanical stretching in Muller cells. Rat Muller cells were seeded onto flexible bottom culture plates and subjected to a cyclic stretching regimen of 15% equibiaxial stretching for 1 and 24 h.Muller cells cultured under the same conditions but with no applied mechanical strain were considered as the unstretched control. At each time points (1 and 24 h), three totally independent experiments (3 stretched samples and 3 control samples) were conducted. Muller cells were selected for RNA extraction and hybridization on Affymetrix microarrays. Stretch (S); Control (C)
2013-01-16 | E-GEOD-43516 | biostudies-arrayexpress
Project description:Mechanical stretch induced transcriptomic profiles in cardiac myocytes
| PRJNA419923 | ENA