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GSE26390
Mus musculus
16 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Hypertrophic scar (HTS) formation is characterized by exuberant fibroproliferation for reasons that remain poorly understood1. One important but often overlooked component of wound repair is mechanical force, which regulates reciprocal cell-matrix interactions through focal adhesion components including focal adhesion kinase (FAK)1,2. Here we report that FAK is activated following cutaneous injury and that this activation is potentiated by mechanical loading. Transgenic mice lacking fibroblast-specific FAK exhibit significantly less fibrosis in a preclinical model of HTS formation. Inflammatory pathways involving monocyte chemoattractant protein-1 (MCP-1), a chemokine highly implicated in human skin fibrosis3, are triggered following FAK activation, mechanistically linking physical force to fibrosis. Further, small molecule inhibition of FAK effectively abrogates fibroproliferative mechanisms in human cells and significantly reduces scar formation in vivo. Collectively, these findings establish a molecular basis for HTS formation based on the mechanical activation of fibroblast-specific FAK and demonstrate the therapeutic potential of targeted mechanomodulatory strategies.
Publication Title
Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The estrogen-dependence of breast cancer has long been recognized, however, the role of 17-estradiol (E2) in cancer initiation was not known until we demonstrated that it induces complete neoplastic transformation of the human breast epithelial cells MCF-10F. E2-treatment of MCF-10F cells progressively induced high colony efficiency and loss of ductulogenesis in early transformed (trMCF) cells and invasiveness in Matrigel invasion chambers. The cells that
Publication Title
Epithelial to mesenchymal transition in human breast epithelial cells transformed by 17beta-estradiol.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
Skeletal muscle of insulin resistant individuals is characterized by lower fasting lipid oxidation and reduced ability to switch between lipid and glucose oxidation. The purpose of the present study was to examine if impaired metabolic switching could be induced by chronic hyperglycemia. Human myotubes were treated with or without chronic hyperglycemia (HG) (20 mmol/l glucose for 4 days), and the metabolism of [14C]oleic acid (OA) and [14C]glucose was studied. Acute glucose (5mmol/l) suppressed OA oxidation by 50% in normoglycemic (NG) (5.5 mmol/l glucose) cells. Myotubes exposed to chronic hyperglycemia showed a significantly reduced OA uptake and oxidation to CO2, whereas acid-soluble metabolites were increased. Glucose suppressibility, the ability of acute glucose to suppress lipid oxidation, was significantly reduced to 21%, while adaptability, the capacity to increase lipid oxidation with increasing fatty acid availability, was unaffected. Glucose uptake and oxidation was significantly reduced by about 40%. Substrate oxidation in presence of mitochondrial uncouplers showed that net and maximal oxidative capacities were significantly reduced after hyperglycemia, and the concentration of ATP was reduced by 25%. However, none of the measured mitochondrial genes were downregulated nor was mitochondrial content. Microarray showed that no genes were significantly regulated by chronic hyperglycemia. Addition of chronic lactate reduced both glucose and OA oxidation to the same extent as hyperglycemia, and this effect was specific for lactate. In conclusions, chronic hyperglycemia reduced substrate oxidation in skeletal muscle cells and impaired the metabolic switching. The effect is most likely due to an induced mitochondrial dysfunction.
Publication Title
Chronic hyperglycemia reduces substrate oxidation and impairs metabolic switching of human myotubes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
The aim of the present work was to study the effects of benfotiamine (S-benzoylthiamine O-monophosphate) upon glucose and lipid metabolism and gene expression in differentiated human skeletal muscle cells (myotubes) incubated for 4 days under normal (5.5 mM glucose) and hyperglycemic (20 mM glucose) conditions.
Publication Title
Benfotiamine increases glucose oxidation and downregulates NADPH oxidase 4 expression in cultured human myotubes exposed to both normal and high glucose concentrations.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The role of peroxisome proliferator-activated receptor (PPAR) activation on global gene expression and mitochondrial fuel utilization were investigated in human myotubes. Only 21 genes were up-regulated and 3 genes were down-regulated after activation by the PPAR agonist GW501516. Pathway analysis showed up-regulated mitochondrial fatty acid oxidation, TCA cycle and cholesterol biosynthesis. GW501516 increased oleic acid oxidation and mitochondrial oxidative capacity by 2-fold. Glucose uptake and oxidation were reduced, but total substrate oxidation was not affected, indicating a fuel switch from glucose to fatty acid. Cholesterol biosynthesis was increased, but lipid biosynthesis and mitochondrial content were not affected. This study confirmed that the principal effect of PPAR activation was to increase mitochondrial fatty acid oxidative capacity. Our results further suggest that PPAR activation reduced glucose utilization through a switch in mitochondrial substrate preference by up-regulating pyruvate dehydrogenase kinase isozyme 4 and genes involved in lipid metabolism and fatty acid oxidation.
Publication Title
PPARδ activation in human myotubes increases mitochondrial fatty acid oxidative capacity and reduces glucose utilization by a switch in substrate preference.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We sought to elucidate the molecular mechanisms whereby LIN28B functions by comparing the gene expression profile of cells constitutively expressing LIN28B to empty vector controls.
Publication Title
LIN28B promotes colon cancer progression and metastasis.
Sample Metadata Fields
Disease, Cell line
View Samples- Homo sapiens
- 110 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
It is widely accepted that a womans lifetime risk of developing breast cancer at menopause is reduced by early full term pregnancy and multiparity. This phenomenon is associated with the development and differentiation of the breast, which ultimately imprints a specific genomic profile in the mammary epithelium. In the present work we demonstrate that this profile represents a permanent signature that could be associated with the breast cancer risk reduction conferred by pregnancy.
Publication Title
Defining the genomic signature of the parous breast.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
To begin to identify genes involved in the transdifferentiation process we analyzed Barretts esophagus (with no dysplasia), normal esophagus and small intestine biopsy samples by Affymetrix microarray.
Publication Title
Cdx1 and c-Myc foster the initiation of transdifferentiation of the normal esophageal squamous epithelium toward Barrett's esophagus.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The heterogeneous collection of NuRD complexes can be grouped into the MBD2 or MBD3 containing complexes MBD2-NuRD and MBD3-NuRD. MBD2 is known to bind to methylated CpG sequences in vitro in contrast to MBD3. Although functional differences have been described, a direct comparison of MBD2 and MBD3 in respect to genome-wide binding and function has been lacking. Here we show when depleting cells for MBD2, the MBD2 bound genes increase their activity, whereas MBD2 plus MBD3 bound genes reduce their activity. Most strikingly, MBD3 is enriched at active promoters, whereas MBD2 is bound at methylated promoters and enriched at exon sequences of active genes. This suggests a functional connection between MBD2 binding to chromatin and splicing.
Publication Title
Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences.
Sample Metadata Fields
Cell line
View Samples