BRAF inhibitors are highly effective therapies for patients with BRAF V600 mutated metastatic melanoma. Patients who receive BRAF inhibitors develop a variety of hyper-proliferative skin conditions, whose pathogenic basis is the paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway in BRAF wild-type cells. Most of these hyper-proliferative skin changes improve when a MEK inhibitor is co-administered, as a MEK inhibitor blocks paradoxical MAPK activation. We tested whether we could take advantage of the mechanistic understanding of the skin hyper-proliferative side effects of BRAF inhibitors to accelerate skin wound healing by inducing paradoxical MAPK activation. Here we show that the BRAF inhibitor vemurafenib accelerates human keratinocyte proliferation and migration by increasing ERK phosphorylation and cell cycle progression. Topical treatment with vemurafenib in two wound-healing models in mice accelerated cutaneous wound healing and improved the tensile strength of healing wounds through paradoxical MAPK activation; addition of a MEK inhibitor reversed the benefit of vemurafenib-accelerated wound healing. The same dosing regimen of topical BRAF inhibitor did not increase the incidence of cutaneous squamous cell carcinomas in mice even after the application of a carcinogen. Therefore, topical BRAF inhibitors may have clinical applications in accelerating the healing of skin wounds. Overall design: Full depth incisional wound mice tissues with/without Vemurafenib treatment were sent for RNAseq analysis on day 2, 6 and 14
Cutaneous wound healing through paradoxical MAPK activation by BRAF inhibitors.
Specimen part, Subject
View SamplesCFU-PreB colonies are reduced in number and size in Hspa9+/- mice compared to wildtype littermates. We compared the expression profiles of these colonies to gain insight into the mechanism driving this difference.
Reduced levels of Hspa9 attenuate Stat5 activation in mouse B cells.
Specimen part
View SamplesThere is an association between transcriptome and the exercise-related phenotype. Peripheral blood cells suffer alterations in the gene expression pattern in response to perturbations caused by exercise. The acute response to endurance activates stress and inflammation, as well as growth and tissue repair responses.
PBMCs express a transcriptome signature predictor of oxygen uptake responsiveness to endurance exercise training in men.
Sex, Specimen part, Disease, Disease stage, Treatment, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Silencing the Snail-Dependent RNA Splice Regulator ESRP1 Drives Malignant Transformation of Human Pulmonary Epithelial Cells.
Age, Specimen part
View SamplesA limited number of growth factors are capable of regulating numerous developmental processes, but how they accomplish this is unclear. In the gustatory system, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4) have different developmental roles but exert their effects through the same receptors (TrkB and p75).
BDNF and NT4 play interchangeable roles in gustatory development.
Specimen part
View SamplesThe root apex is an important section of the plant root, involved in environmental sensing and cellular development. Analyzing the gene profile of root apex in diverse environments is important and challenging, especially when the samples are limiting and precious, such as in spaceflight. The feasibility of using tiny root sections for transcriptome analysis was examined in this study.To understand the gene expression profiles of the root apex, Arabidopsis thaliana Col-0 roots were sectioned into Zone-I (0.5 mm, root cap and meristematic zone) and Zone-II (1.5 mm, transition, elongation and growth terminating zone). Gene expression was analyzed using microarray and RNA seq.Both the techniques, arrays and RNA-Seq identified 4180 common genes as differentially expressed (with > two-fold changes) between the zones. In addition, 771 unique genes and 19 novel TARs were identified by RNA-Seq as differentially expressed which were not detected in the arrays. Single root tip zones can be used for full transcriptome analysis; further, the root apex zones are functionally very distinct from each other. RNA-Seq provided novel information about the transcripts compared to the arrays. These data will help optimize transcriptome techniques for dealing with small, rare samples. Overall design: Arabidopsis thaliana var. Columbia (COL-0) seedlings were grown on sterile solid media plates containing 0.5 % phytagel. The plates were vertically placed in growth chambers with continuous light (80-100 µmol m -2) at a constant temperature of 19° C. Eight day old seedlings were harvested into RNA-later solution in a 50 mL centrifuge tubes and stored at -20 °C freezer. The root tips were dissected into zone-I: 0.5mm from the tip including the root cap and root division zones, and zone-II: 1.5mm sections including root elongation and root hair zone. Microarray and sequencing experiments were performed.
Comparing RNA-Seq and microarray gene expression data in two zones of the <i>Arabidopsis</i> root apex relevant to spaceflight.
Age, Specimen part, Subject
View SamplesA growing body of evidence suggests that the vasoactive peptides endothelins (ETs) and their receptors (primarily the ETB receptor) are contributors to neurodegeneration in glaucoma. However, ETs actions in retinal ganglion cells (RGCs) are not fully understood. The purpose of this study was to determine ETs effects on gene expression in primary RGCs.
Endothelin-Mediated Changes in Gene Expression in Isolated Purified Rat Retinal Ganglion Cells.
Specimen part
View SamplesGenome-wide transcriptome analysis was carried out in root tissue of Arabidopsis seedlings treated with gold (Au) as Chloroauric acid (HAuCl4). This study demonstrated remarkable changes in root transcriptome within the 12 h exposure. Most of the genes differentially expressed were related to glutathione binding, methylations, secondary metabolism, sugar metabolism, ABA, ethylene, auxin related signalling, transport and signal-transduction pathways.
Genome wide transcriptome analysis reveals ABA mediated response in Arabidopsis during gold (AuCl(-) 4) treatment.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comparing RNA-Seq and microarray gene expression data in two zones of the <i>Arabidopsis</i> root apex relevant to spaceflight.
Age, Specimen part
View SamplesGlobal analysis of brassinosteroid (BR)-mediated gene expression under abiotic stress identifies BR associated mechanisms of stress tolerance, and new stress-related genes
Gene expression and functional analyses in brassinosteroid-mediated stress tolerance.
Age, Specimen part
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