Cyclic mechanical stretch-induced gene expression
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Maria Reichenbach
PROVIDER: E-GEOD-58389 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
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:Background: Basal cells within the human airway epithelium constitute the stem/progenitor cells for other epithelial cell types. Basal cells respond to mucosal injury and damage to the airway mucosa in an ordered sequence of spreading, migration, proliferation and phenotype shifting (differentiation) to other needed cell types. However, dynamic gene transcription in the early events of injury and repair has not been examined in these cells. Methodology and findings: Airway epithelial cells were obtained from donated lungs and grown in submersion culture on pliable membranes to obtain a pure population of basal cells. Microarrays were used to assess the transcriptome of basal cells 8 and 24 hr after mechanical injury (MI), or to cyclic stretch (CS) in a Flexcell system (0.5 Hz, 20% distension), or both treatments. We identified 121 signature genes with > 2-fold higher differential expression (DE) 8 hr after MI; expression of nearly all of these genes returned to baseline at 24 hr after injury. In cells subjected to CS, little change in DE was noted at 8 hr, whereas at 24 hr a CS signature of 1430 DE genes were identified. The MI signature was characterized by genes encoding growth factor receptors related to the EGF pathway, IL-6, IL-8 and IL-33, extracellular matrix components, and NF-kB and p38-MAPK signaling pathways, whereas the CS signature was characterized by a broad range of genes that did not identify specific signaling pathways. Combined MI and CS at 8 hr elicited DE of down-regulated genes not seen with either stimulus alone, and at 24 hr elicited DE that was similar to that seen with CS alone. Conclusion and significance: The human airway basal epithelial cell transcription signature in the first hours after MI, after CS, and after both stimuli identifies unique differentially expressed genes and pathways that may be important in the early molecular response and biology to airway injury. Total RNA obtained from primary (AEC) and differentiated (dAEC) human airway epithelial cells subjected to 8 or 24 hours in vitro mechanical or cyclic stretch or both injuries compared to sham control as well as to type of injury. Cells were collected from four donated lungs and cultured separated in submission or air liquid interface condition prior to injury for various durations.
2015-04-30 | E-GEOD-59128 | biostudies-arrayexpress
Project description:Aortic valve calcification is a significant and serious clinical problem for which there are no effective medical treatments. Individuals born with bicuspid aortic valves, 1-2% of the population, are at the highest risk of developing aortic valve calcification. Aortic valve calcification involves increased levels of calcification and inflammatory genes. Bicuspid aortic valve leaflets experience increased strain. The molecular mechanisms involved in the pathogenesis of calcification of BAVs are not well understood, especially the molecular response to mechanical stretch. HOTAIR is a long non-coding RNA (lncRNA) that has been implicated with cancer but has not been studied in cardiac disease. We have found that HOTAIR levels are decreased in BAVs and in human aortic interstitial cells (AVICs) exposed to cyclic stretch. Reducing HOTAIR levels via siRNA in AVICs results in increased expression of calcification genes.
2014-05-02 | E-MTAB-2409 | biostudies-arrayexpress
Project description:Differentiated PC12 cells were magnetically labeled with magnetic nanoparticles (MNP). External magnetic fields were used to mechanically stretch the MNP-labeled neurites. We found that mechanical stretching of the neurites induces mass addition and neurite elongation. We performed RNAseq of MNP-labelled cells in stretched versus non-stretched conditions and we did not found gene expression dysregulation, confirming that the two conditions were identical and excluding cytotoxicity or involvement of nuclear mechanotransdution. Indeed, local mechanisms triggered by the stretching of the MNP-labelled neurite would be responsible for neurite elongation.
2018-06-08 | GSE115474 | GEO
Project description:Mechanical stress is a potent regulator of cell growth, contractility and gene regulation. Abnormal uterine distension during pregnancy increases the risk of preterm birth and likely activates crosstalk between multiple signaling networks with protein phosphorylation playing a critical role. Telomerized human uterine smooth muscle cells were exposed to 18% biaxial stretch for 5 min and the phosphoproteome was probed by mass spectrometry. We observed specific phospho-activation of mitogen activated protein kinase at threonine 183 and tyrosine 185, myosin regulatory light chain 9 at threonine 19, and heat shock protein 27 at serine 82. Our analysis revealed protein phosphorylation changes in signaling pathways related to actin cytoskeleton remodeling, activation of the focal adhesion kinase pathway, smooth muscle contraction and mechanistic target of rapamycin activation. These data point to potential mechanistic links between stretch-induced phosphorylation and development of the contractile phenotype in myometrial cells.
2019-04-10 | PXD002538 | Pride
Project description:Current knowledge of mechanically-induced regulation of gene expression in fibroblast is mostly based on experiments using prolonged cyclical stretching of either cultured cells or load-bearing connective tissues such as tendons and ligaments. In this study, we have examined the effect of static tissue stretch on fibroblasts within loose connective tissue using in vivo and ex vivo models. In an in vivo trunk side bending model, one side of the trunk of the mouse was stretched while the other side was shortened under anesthesia for 90 minutes. In the ex vivo method, whole subcutaneous tissue explants (including skin, subcutaneous muscle and subcutaneous tissue) from both sides of the trunk were incubated ex vivo either stretched or not stretched (shortened) for 24 hours. Tissue stretch or shortening was followed by immediate dissection of the loose connective tissue layer on both sides of the trunk, RNA extraction and gene expression analysis using Affymetrix mouse gene arrays. In both in vivo and ex vivo experiments, a large cluster of genes related to skeletal muscle function and carbohydrate metabolism was up-regulated in the stretched, compared with the shortened, connective tissue samples. However, there were few differentially expressed matrix-related genes, and in particular no change in collagen genes. Immunohistochemical staining for myosin after tissue stretch for 24 hours ex vivo showed increased myosin immunoreactivity in fibroblasts within the stretched compared with the shortened tissue samples. These results suggest that dynamic modulation of muscle-related gene expression is a normal physiological response of loose connective tissue fibroblasts to changes in tissue length.. Keywords: response to mechanical stretch Within animal stretched vs shortened (randomized): 7 animals in vivo and 4 ex vivo.
2011-05-08 | E-GEOD-11371 | biostudies-arrayexpress
Project description:Context: Increased uterine stretch appears to increase the risk of preterm labour, but the mechanism is unknown. Objectives: To identify a targetable mechanism mediating the effect of stretch on human myometrium. Design: Myometrial explants, prepared from biopsies obtained at elective caesarean delivery, were either studied acutely, or were maintained in prolonged culture (up to 65 h) under tension with either a 0.6 g or 2.4 g mass, and compared using in vitro contractility, whole genome array, and qRT-PCR. Results: Increased stretch for 24 or 65 h increased potassium-induced and oxytocin-induced contractility. Gene array identified 62 differentially expressed transcripts after 65 h exposure to increased stretch. Two probes for gastrin-releasing peptide (GRP), a known stimulatory agonist of smooth muscle, were among the top five up-regulated by stretch (3.4-fold and 2.0-fold). Up-regulation of GRP by stretch was confirmed in a separate series of 10 samples using qRT-PCR (2.8-fold, P = 0.01). GRP stimulated contractions acutely when added to freshly obtained myometrial strips in 3 out of 9 cases, but Western blot demonstrated expression of the GRP receptor in 9 out of 9 cases. Prolonged incubation of stretched explants in the GRP antagonists PD-176252 or RC-3095 (65 and 24 h respectively) significantly reduced potassium chloride and oxytocin-induced contractility. Conclusion: Stretch of human myometrium increases contractility and stimulates the expression of a known smooth muscle stimulatory agonist, GRP. Incubation of myometrium in GRP receptor antagonists ameliorates the effect of stretch. GRP may be a target for novel therapies to reduce the risk of preterm birth in multiple pregnancy. 9 paired samples of human myometrium cultured under low (0.6g) or high (2.4g) tension
2012-06-14 | E-GEOD-31329 | biostudies-arrayexpress
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:Lung cancer is one of the leading causes of death. However, most of the researches were based on the traditional cell-culturing method. Whereas cells of lung are subjected to the mechanical forces periodically while breathing. In the present study, we applied cyclic stretch to stimulate the continuously contracting physical condition. We uncovered the stretching force-induced phosphoproteome in lung cancer cell A549 and fibroblast IMR-90. 2048 and 2604 phosphosites corresponding to 837 and 1008 phosphoproteins were identified in A549 and IMR-90, respectively. Interestingly, cytoskeleton reorganization and mitochondrial localization were enriched in the significantly expressed phosphoproteins in response to cyclic stretch. Indeed, we found this physical stress changed cell alignment thus disrupted mitochondrial dynamics. We proved that mitochondrial fusion is induced by uniaxial stretch in 2 cell lines. This study reveals the molecular mechanism of cyclic stretch and supports that stretching force enhanced cellular rearrangement and mitochondrial fusion in lung cells.
2021-09-08 | PXD012010 | Pride
Project description:Current knowledge of mechanically-induced regulation of gene expression in fibroblast is mostly based on experiments using prolonged cyclical stretching of either cultured cells or load-bearing connective tissues such as tendons and ligaments. In this study, we have examined the effect of static tissue stretch on fibroblasts within loose connective tissue using in vivo and ex vivo models. In an in vivo trunk side bending model, one side of the trunk of the mouse was stretched while the other side was shortened under anesthesia for 90 minutes. In the ex vivo method, whole subcutaneous tissue explants (including skin, subcutaneous muscle and subcutaneous tissue) from both sides of the trunk were incubated ex vivo either stretched or not stretched (shortened) for 24 hours. Tissue stretch or shortening was followed by immediate dissection of the loose connective tissue layer on both sides of the trunk, RNA extraction and gene expression analysis using Affymetrix mouse gene arrays. In both in vivo and ex vivo experiments, a large cluster of genes related to skeletal muscle function and carbohydrate metabolism was up-regulated in the stretched, compared with the shortened, connective tissue samples. However, there were few differentially expressed matrix-related genes, and in particular no change in collagen genes. Immunohistochemical staining for myosin after tissue stretch for 24 hours ex vivo showed increased myosin immunoreactivity in fibroblasts within the stretched compared with the shortened tissue samples. These results suggest that dynamic modulation of muscle-related gene expression is a normal physiological response of loose connective tissue fibroblasts to changes in tissue length.. Keywords: response to mechanical stretch
2011-05-08 | GSE11371 | GEO