The ion channel Trpc6a regulates the cardiomyocyte regenerative response to mechanical stretch
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB70944 | ENA |
REPOSITORIES: ENA
Similar Datasets
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:Tissues and cells in organism are continuously exposed to a complicated set of mechanical cues from the environment. Mechanical stimulations affect cell proliferation, differentiation, migration, and determine tissue homeostasis as well as repair. By using a specially designed skin-stretching device, we discover hair stem cells proliferate in response to stretch and hair regeneration occurs only when proper strain and duration were delivered. Counterbalance between WNT and BMP-2 followed by a two-step mechanism was identified through molecular and genetic analyses. Macrophages were first recruited by chemokines elicited by stretch and polarized to M2 phenotype. Growth factors such as HGF and IGF-1 released by M2 macrophages then activated hair stem cells and facilitate hair regeneration. Collectively, a hierarchical control from mechanics, chemical signals, cell behaviors, to tissue responses was revealed. This novel finding shed new light on regenerative medicine and disease control since one can manipulate cellular processes through simple mechanical stimulation.
2019-01-30 | GSE125806 | GEO
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:Alveolar epithelial type II (AEII) cells are the first line host in response to mechanical ventilation. We tested the hypothesis that the modulation of microRNA on AEII cells in response to mechanical stretch may participate in the ventilator-induced lung injury. This experiment is designed to screen miRNAs that are deregulated during mechanical stretch of AEII cells.
2015-11-18 | GSE75100 | GEO
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:Mechanical stretch induced transcriptomic profiles in cardiac myocytes
| PRJNA419923 | ENA
Project description:Analysis of gene expression patterns in enlarged left atrial appendage (LAA) in mitral/aortic valve replacement or coronary artery bypass graft surgery can help to identify a comprehensive panel of gene biomarkers for predicting clinical outcomes and to discover potential new therapeutic targets. However, the transcriptional profiles triggered by extended mechanical stretch in cardiac myocytes are not fully understood. Here we performed the first genome-wide study of gene expression changes in human enlarged left atium, resulting in 335 differentially expressed (> 2-fold, P < 0,05) genes in response to mechanical stretch.
2021-01-12 | GSE125094 | GEO
Project description:The extracellular matrix (ECM) initiates mechanical cues and transduces intracellular signaling through matrix-cell interactions. The nature of cues and how they coordinate with a mechanical microenvironment are not fully understood. We identified the matricellular protein, thrombospondin-1 (Tsp1, also called Thbs1), as a mediator of matrix mechanotransduction that acts via integrin αvβ1 to establish focal adhesions and promotes nuclear shuttling of Yes-associated protein (YAP) in response to cyclic stretch. Thbs1-mediated YAP activation depends on the small GTPase Rap2 and Hippo pathway, and is not influenced by altered actin fibers. Hence, to gain insight into the molecular mechanisms underlying the Tsp1-mediated matrix mechanotransduction, we performed a comprehensive analysis of gene expression changes in Tsp1deficiant SMCs with mechanical stretch using RNA sequencing (RNA-Seq).
2020-03-17 | GSE131750 | GEO
Project description:Mechanical stretch induced transcriptomic profiles in cardiac myocytes II
| PRJNA420515 | ENA