CELL CONTRACTILITY AND AN ACTIN GRADIENT DRIVE POLAR ALIGNMENT OF FIBROBLASTS IN CONSTRAINED GEOMETRIES
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PROVIDER: PRJNA623348 | ENA |
REPOSITORIES: ENA
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Project description:When REF 2c cells were placed on circular micro-contact printed patterns, the boundary cells radially aligned over a period of 48 h. Video tracking of specific boundary and inner cells showed that this phenomenon was not caused by cells migrating towards or away from the periphery. Cell contractility, intercellular junctions, and cell-cell adhesion are required for radial alignment.
2020-04-07 | GSE148155 | GEO
Project description:The shear stress-induced transcription factor Krüppel-like factor 2 (KLF2) confers anti-inflammatory properties to endothelial cells through inhibition of activator protein 1, presumably by interfering with MAPK cascades. To gain insight into the regulation of these cascades by KLF2, we used antibody arrays in combination with time-course mRNA micro-array analysis. No gross changes in MAPKs were detected, rather phosphorylation of actin cytoskeleton-associated proteins, including Focal Adhesion Kinase, was markedly repressed by KLF2. Furthermore, we demonstrate that KLF2-mediated inhibition of Jun NH2-terminal kinase (JNK) and its downstream targets ATF2/c-Jun is dependent on the cytoskeleton. Specifically, KLF2 directs the formation of typical short basal actin filaments, we term shear fibers, which are distinct from thrombin- or TNF-α-induced stress fibers. KLF2 is shown to be essential for shear stress-induced cell alignment, concomitant shear fiber assembly and inhibition of JNK signaling. These findings link the specific effects of shear-induced KLF2 on endothelial morphology to the suppression of JNK MAPK signaling in vascular homeostasis via novel actin shear fibers.
2009-12-11 | GSE19412 | GEO
Project description:The shear stress-induced transcription factor Krüppel-like factor 2 (KLF2) confers anti-inflammatory properties to endothelial cells through inhibition of activator protein 1, presumably by interfering with MAPK cascades. To gain insight into the regulation of these cascades by KLF2, we used antibody arrays in combination with time-course mRNA micro-array analysis. No gross changes in MAPKs were detected, rather phosphorylation of actin cytoskeleton-associated proteins, including Focal Adhesion Kinase, was markedly repressed by KLF2. Furthermore, we demonstrate that KLF2-mediated inhibition of Jun NH2-terminal kinase (JNK) and its downstream targets ATF2/c-Jun is dependent on the cytoskeleton. Specifically, KLF2 directs the formation of typical short basal actin filaments, we term shear fibers, which are distinct from thrombin- or TNF-α-induced stress fibers. KLF2 is shown to be essential for shear stress-induced cell alignment, concomitant shear fiber assembly and inhibition of JNK signaling. These findings link the specific effects of shear-induced KLF2 on endothelial morphology to the suppression of JNK MAPK signaling in vascular homeostasis via novel actin shear fibers. Tramscriptome profiling: Three independent isolates of Human Umbilical Vein Endothelial cells were transduced with lentiviral vectors expressing Kruppel Like Factor 2 (KLF2) or no protein (mock), and at time after transduction 24 h, 48 h, 72 h , RNA was isolated and hybridized to GPL4868 microarrays using dye swap procedure Kinome profiling: Two independent isolates of Human Umbilical Vein Endothelial cells were transduced with lentiviral vectors expressing Kruppel Like Factor 2 (KLF2) or no protein (mock), and at time after transduction 72 h , total cellular protein was isolated and hybridized to Kinexus KAM-1.1 phosphoprotein (kinexus) microarrays using dual color procedure in duplicate
2010-06-25 | E-GEOD-19412 | biostudies-arrayexpress
Project description:Actomyosin contractility regulates cell morphology and movement. The objective of this study was to identify whether actomyosin contractility regulates gene expression in tumour cells and whether such genes are involved in cell morphology and movement. Gene expression analysis was carried out on highly contractile melanoma cell line A375M2 plated on a deformable collagen matrix under conditions where actomyosin contractility could be altered following treatment with blebbistatin, a direct inhibitor of myosin II, or Rho-kinase inhibitors Y27632 or H1152 that interfere with signalling to myosin II. 18 samples (6 x 3 biological replicates). Cells were plated on rigid or deformable matrices. Rounded cells (A375M2 melanoma cells) plated on deformable matrices were left untreated or treated with Rho-kinase inhibitors Y27632, H1152 or blebbistatin an inhibitor of mysoin II.
2010-08-24 | E-GEOD-23764 | biostudies-arrayexpress
Project description:Actomyosin contractility regulates cell morphology and movement. The objective of this study was to identify whether actomyosin contractility regulates gene expression in tumour cells and whether such genes are involved in cell morphology and movement. Gene expression analysis was carried out on highly contractile melanoma cell line A375M2 plated on a deformable collagen matrix under conditions where actomyosin contractility could be altered following treatment with blebbistatin, a direct inhibitor of myosin II, or Rho-kinase inhibitors Y27632 or H1152 that interfere with signalling to myosin II.
2010-08-24 | GSE23764 | GEO
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Project description:Deoxynivalenol (DON) is one of the frequent Fusarium mycotoxins and poses a serious threat to public health worldwide, especially in humans and pigs. Growth retardation is the critical symptom of DON poisoning, commonly manifested by weight loss and reduced food intake. The gastrointestinal tract (GIT) is the principal target organ in the body and DON-induced weight loss is tightly connected with its capacity to reduce feed intake by disturbing the GIT motility. Our previous reports for the first time indicated that DON interfered with intestinal motility by injuring the contractility of enteric smooth muscle cells (SMC), suggesting that enteric SMC might be a main target in the procession of DON-induced GIT motility disorder. However, underlying molecular mechanisms of DON-induced enteric SMC contractile dysfunction remain poorly understood until now. Here, we explored the potential molecular mechanisms by employing a complementary method of transcriptomics and proteomics using the porcine enteric smooth muscle cell line (PISMC) as an experimental model. First, the DON-induced contractile dysfunction of the enteric SMC model was successfully established with PISMC, which was evidenced by decreased cell contractility, cell viability, and the expression levels of SMC contractile markers (contractile apparatus components). Subsequently, transcriptomic and proteomic analyses were used to reveal the differentially expressed gene and protein profiles after DON exposure. A total of 2944 genes and 980 proteins were identified as differentially expressed. Additionally, a systematic bioinformatic analysis of gene-protein interactions revealed that a total of 152 co-differentially expressed genes were identified. The data uncover that the expression of numerous extracellular matrix (ECM) proteins was downregulated in PISMC under DON exposure. DON also remarkably decreased the expression of multiple integrin subunits, resulting in the inhibition of the ECM-integrin receptor interaction and its mediated signaling. Furthermore, DON treatment could depress actin polymerization, as reflected by the upregulated expression of Rho GTPase-activating proteins, cofilin and the downregulated expression levels of Rho guanine nucleotide exchange factors in PISMC. Meanwhile, the expression levels of downstream target genes that were responsible for sustaining contractile phenotype were significantly inhibited in PISMC challenge with DON, including actin alpha 2, caldesmon 1, and myosin regulatory light chain 9 and so on. Taken together, the current results suggest that DON inhibits enteric smooth muscle cell contractility via regulating the ECM-integrin-actin polymerization signaling pathway mediated downstream contractile apparatus genes expression. Our findings provide novel insights into potential mechanisms behind the DON toxicological effects in the GIT of humans and animals.
2023-03-06 | PXD040605 | iProX
Project description: Not available
| S-EPMC8478414 | biostudies-literature
Project description:Cell function depends on the mechanical properties of the microenvironment. Cells probe these features by applying and transmitting forces to their surroundings, via their actomyosin cytoskeleton and adhesion complexes, and then transducing them into biochemical signals. Among these, the transcriptional coactivators YAP/TAZ recently emerged as key factors mediating some biological responses to actomyosin contractility in vitro. However, whether mechanical cues regulate YAP/TAZ activity in vivo, and whether this is relevant for adult tissue homeostasis, remains poorly understood. Here we show that the F-actin capping protein CAPZ is a critical regulator of actomyosin contractility, as its inactivation alters stress fiber and focal adhesion dynamics, leading to enhanced myosin activity and increased cellular traction forces. In vitro, this rescues YAP from inhibition by a small geometry; in vivo, inactivation of Capzb in the mouse liver induces YAP activation and hepatocyte proliferation, leading to striking organ overgrowth. Moreover, Capzb is essential for the maintenance of the differentiated hepatocyte state, and for the metabolic zonation of hepatocytes. In keeping with changes in tissue mechanics and activation of YAP, inhibition of ROCK or deletion of Yap1 reverse the phenotypes emerging in Capzb-null livers. These results indicate a previously unrecognized role for CAPZ in tuning the sensitivity of cells and tissues to mechanical signals, and a physiological function for F-actin dynamics in regulating organ growth and tissue homeostasis.
2019-03-19 | GSE116993 | GEO