Role of zyxin in the tension-induced expression change in endothelial cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE17814 | GEO | 2010/08/16
SECONDARY ACCESSION(S): PRJNA120123
REPOSITORIES: GEO
Similar Datasets
Project description:One of the hallmarks in hypertension is a pressure-induced change in endothelial cell phenotype. A cytoskeletal protein zyxin, which was seen to translocate from focal adhesion contacts to the nucleus in response to the increased wall tensionis, mediates the tension-induced endothelial signaling. Microarrays were used to detail the role of zyxin in the tension-induced expression changes in endothelial cells. Primary endothelial cells (Huvec) from four treatment groups were used for RNA extraction and hybridization on Affymetrix microarrays: wild type under normal condition, wild type under tension, Zyxin-SiRNA-treated under normal condition and Zyxin-SiRNA-treated under tension.
2010-08-16 | E-GEOD-17814 | biostudies-arrayexpress
Project description:Hypertrophic scars arise from dysregulated wound healing under prolonged mechanical tension, causing disfiguring fibrosis. However, limited preclinical models replicate key features of human tension-induced scarring. We developed an innovative murine model utilizing suture anchoring to impose persistent transverse-axial stretch across healing incisions, mimicking excessive wound tension that leads to hypertrophy clinically. Dorsal paired incisions were generated in mice, with wound edges on the upper back sutured to the rib cage while leaving wound edges on the lower back relaxed. This localized anchoring restrained wound contraction, maintaining high tension throughout remodeling analogous to scars widening under stress. Stretched upper wounds developed profound fibrotic changes compared to relaxed controls. Scars induced by suture-anchored tension displayed macroscopic hypertrophy, hardness, erythema, and pruritis up to 3 months. Histologically, scars induced by suture-anchored tension were hypercellular, hypervascular, hyperproliferative with disorganized extracellular matrix deposition, and displayed molecular hallmarks of hypertrophic fibrosis. MiRNA sequencing revealed the different signature in suture-anchored tension induced hypertrophic scars compared to control normal scars.
2023-09-28 | GSE243948 | GEO
Project description:Hypertrophic scars arise from dysregulated wound healing under prolonged mechanical tension, causing disfiguring fibrosis. However, limited preclinical models replicate key features of human tension-induced scarring. We developed an innovative murine model utilizing suture anchoring to impose persistent transverse-axial stretch across healing incisions, mimicking excessive wound tension that leads to hypertrophy clinically. Dorsal paired incisions were generated in mice, with wound edges on the upper back sutured to the rib cage while leaving wound edges on the lower back relaxed. This localized anchoring restrained wound contraction, maintaining high tension throughout remodeling analogous to scars widening under stress. Stretched upper wounds developed profound fibrotic changes compared to relaxed controls. Scars induced by suture-anchored tension displayed macroscopic hypertrophy, hardness, erythema, and pruritis up to 3 months. Histologically, scars induced by suture-anchored tension were hypercellular, hypervascular, hyperproliferative with disorganized extracellular matrix deposition, and displayed molecular hallmarks of hypertrophic fibrosis. MRNA sequencing revealed the fibrogenic signature in suture-anchored tension induced hypertrophic scars, which exhibited transcriptional overlap with mechanically-stretched scars, human hypertrophic and keloid scars.
2023-09-28 | GSE243949 | GEO
Project description:Endothelial cell (EC) attachment to the matrix and adjacent cells generates a mechanical environment that maintains a restrictive barrier against the uncontrolled influx of circulating protein and immune cells. Mechanisms that mediate the transition from restrictive to leaky endothelium, a hallmark of tissue injury exemplified by acute lung injury (ALI), remain elusive. Here, we show that FAK sensing and transmission of mechanical tension to the EC nucleus governs cell fate. In FAK-deleted EC, increased EC tension activated DNMT3a, which induced methylation of the KLF2 promoter leading to impaired synthesis of KLF2 and restrictive EC transcriptome, including S1PR1. FAK suppressed DNMT3a activity by restricting the tyrosine phosphorylation of nuclear envelope protein, emerin at Y74/Y95, and its localization in a nuclear cap. Inhibiting emerin phosphorylation or DNMT3a activity in damaged lungs enabled KLF2 transcription of S1PR1, rescuing the restrictive EC phenotype. Our works reveal a paradigm whereby FAK sensing of tension transmission to the nucleus maintains restrictive EC transcriptome and lung homeostasis.
2022-08-28 | GSE212037 | GEO
Project description:Cytoskeletal tension is an intracellular mechanism through which cells convert a mechanical signal into a biochemical response, including production of cytokines and activation of various signaling pathways. Adipose-derived stromal cells (ASCs) were allowed to spread into large cells by seeding them at a low-density (1,250 cells/cm2), which was observed to induce osteogenesis. Conversely, ASCs seeded at a high-density (25,000 cells/cm2) featured small cells that promoted adipogenesis. RhoA and actin filaments were altered by changes in cell size. Blocking actin polymerization by Cytochalasin D influenced cytoskeletal tension and differentiation of ASCs. To understand the potential regulatory mechanisms leading to actin cytoskeletal tension, cDNA microarray was performed on large and small ASCs. Connective tissue growth factor (CTGF) was identified as a major regulator of osteogenesis associated with RhoA mediated cytoskeletal tension. Subsequently, knock-down of CTGF by siRNA in ASCs inhibited this osteogenesis. Therefore, we conclude that cytoskeletal tension is important for CTGF-regulated ASC osteogenic differentiation. Computed
2011-01-16 | E-GEOD-19924 | biostudies-arrayexpress
Project description:Cytoskeletal tension is an intracellular mechanism through which cells convert a mechanical signal into a biochemical response, including production of cytokines and activation of various signaling pathways. Adipose-derived stromal cells (ASCs) were allowed to spread into large cells by seeding them at a low-density (1,250 cells/cm2), which was observed to induce osteogenesis. Conversely, ASCs seeded at a high-density (25,000 cells/cm2) featured small cells that promoted adipogenesis. RhoA and actin filaments were altered by changes in cell size. Blocking actin polymerization by Cytochalasin D influenced cytoskeletal tension and differentiation of ASCs. To understand the potential regulatory mechanisms leading to actin cytoskeletal tension, cDNA microarray was performed on large and small ASCs. Connective tissue growth factor (CTGF) was identified as a major regulator of osteogenesis associated with RhoA mediated cytoskeletal tension. Subsequently, knock-down of CTGF by siRNA in ASCs inhibited this osteogenesis. Therefore, we conclude that cytoskeletal tension is important for CTGF-regulated ASC osteogenic differentiation.
2011-01-16 | GSE19924 | GEO
Project description:Podocyte detachment due to mechanical stress is a common issue in hypertension-induced kidney disease. The present study investigated the role of zyxin in mechanically stretched podocytes, a model for glomerular hypertension. Conditionally immortalized differentiated podocytes were seeded on flexible silicon membranes of a six well plate, which was mounted on a manifold connected to a custom-built stretch apparatus (NIPOKA GmbH, Greifswald, Germany), which induced cyclic pressure variations resulting in upward and downward motion of the silicone membranes. We found that zyxin is essential for the adhesion of the postmitotic cell type, the podocytes, in vitro during mechanical stretch as well as in vivo for the maintenance of the kidney filtration.
2024-04-30 | PXD050861 | Pride
Project description:The central nervous system normally functions at O2 levels which would be regarded as hypoxic by most other tissues. However, most in vitro studies of neurons and astrocytes are conducted under hyperoxic conditions without consideration of O2-dependent cellular adaptation. We analyzed the reactivity of astrocytes to 1, 4 and 9% O2 tensions compared to the cell culture standard of 20% O2, to investigate their ability to sense and translate this O2 information to transcriptional activity. Variance of ambient O2 tension for rat astrocytes resulted in profound changes in ribosomal activity, cytoskeletal and energy-regulatory mechanisms and cytokine-related signaling. Clustering of transcriptional regulation patterns revealed four distinct response pattern groups that directionally pivoted around the 4% O2 tension, or demonstrated coherent ascending/decreasing gene expression patterns in response to diverse oxygen tensions. Immune response and cell cycle/cancer-related signaling pathway transcriptomic subsets were significantly activated with increasing hypoxia, whilst hemostatic and cardiovascular signaling mechanisms were attenuated with increasing hypoxia. Our data indicate that variant O2 tensions induce specific and physiologically-focused transcript regulation patterns that may underpin important physiological mechanisms that connect higher neurological activity to astrocytic function and ambient oxygen environments. These strongly defined patterns demonstrate a strong bias for physiological transcript programs to pivot around the 4% O2 tension, while uni-modal programs that do not, appear more related to pathological actions. The functional interaction of these transcriptional ‘programs’ may serve to regulate the dynamic vascular responsivity of the central nervous system during periods of stress or heightened activity.
2012-09-20 | GSE29296 | GEO
Project description:It has been a long-standing challenge to maintain the functions of hepatocytes in vitro. In the present study, we found that mechanical tension-induced yes-associated protein (Yap) activation triggered hepatocyte dedifferentiation. Alleviation of mechanical tension by confinement of cell spreading was sufficient to inhibit hepatocyte dedifferentiation. Based on this finding, we identified a small molecular cocktail LBDXL through reiterative chemical screening that could maintain hepatocyte functions over the long term and in vivo repopulation capacity by targeting actin polymerization and actomyosin contraction.
2019-10-30 | GSE138158 | GEO
Project description:To understand how mechanical cues regulate cell metabolism, we compared early changes in gene expression in Ras-transformed MCF10AtK1 mammary epithelial cells grown in high cytoskeletal tension conditions (plastics) vs. cells grown in low cytoskeletal tension conditions (inhibition of the non-muscle myosin II regulatory kinases ROCK and MLCK with standard small-molecule inhibitors Y27632 and ML7, respectively). Keywords: Expression profiling by array
2019-02-05 | GSE107275 | GEO