Amyotrophic later sclerosis is a motor neuron disease accompanied by metabolic changes. PGC (PPAR gamma coactivator)-1alpha is a master regulator of mitochondrial biogenesis and function and of critical importance for all metabolically active tissues. PGC-1alpha is a genetic modifier of ALS.
ALS-causing mutations differentially affect PGC-1α expression and function in the brain vs. peripheral tissues.
Specimen part
View SamplesSeveral lines of evidence have shown that the endocannabinoid system (ECS) may play a role in the pathophysiology of systemic sclerosis (SSc). Thereby, structurally different dual PPAR?/CB2 agonists such as VCE-004.8 and Ajulemic acid (AjA) have been shown to alleviate skin fibrosis and inflammation in experimental models of SSc. Since both compounds are currently being tested in humans, we were interested to identify similarities and differences in a murine model of SSc. One method available to assess this is the pharmacotranscriptomic signature of the individual compounds. To analyze the pharmacotranscriptomic signature, we used RNA-Seq to analyze the skin gene expression changes from bleomycin-induced fibrosis in mice treated orally with either AjA or EHP-101, a lipidic formulation of VCE-004.8. While both compounds prevented the upregulation of a common group of genes involved in the inflammatory and fibrotic components of the disease and the pharmacotranscriptomic signatures were similar for both compounds in some pathways, we found key differences between the compounds in several functional groups, including genes related the hypoxia, interferon-a and interferon-? response. Additionally, we found 28 specific genes with translation potential by comparing our results with a list of intrinsic human scleroderma genes. Inmunohistochemical analysis revealed that both EHP-101 and AjA prevented bleomycin-induced skin fibrosis, collagen accumulation, and TNC and VCAM expression. However, only EHP-101 normalized the reduced expression of vascular CD31, CD34 and Von Willebrand factor markers, which parallels skin fibrosis, while AjA did not affect these markers. Finally, clear differences were also found in the plasmatic biomarker analysis, in which we found that EHP-101, but not AjA, enhanced the expression of some factors related to angiogenesis and vasculogenesis. Altogether the results indicate that dual PPAR?/CB2 agonists qualify as a novel therapeutic approach for the treatment of SSc and other fibrotic diseases as well, and that EHP-101 has unique mechanisms of action related to the pathophysiology of SSc which could be beneficial in treatment of this complex disease with no current therapeutic options. Overall design: RNA-Seq profiles were generated for six- to eight-week-old female BALB/c mice in four conditions: Control, Bleomycin, Bleomycin + EHP-101 treatment and Bleomycin + Ajulemic acid treatment. Please note that the "raw_counts_newsamples.txt" includes raw counts obtained from featureCounts for the samples included in this entry and the "raw_counts_merged.txt" includes raw counts obtained from merging the counts of the samples from this entry with the counts of the samples from the GSE115503 entry.
Cannabinoid derivatives acting as dual PPARγ/CB2 agonists as therapeutic agents for systemic sclerosis.
Specimen part, Cell line, Subject
View SamplesNotch1 deficient hair matrix keratinocytes have lower mitotic rates, resulting in smaller follicles with fewer cells. In addition, the ratio of melanocytes to keratinocytes is greatly reduced. Microarray was performed to study downstream mechanism of Notch1-deficiency
Bi-compartmental communication contributes to the opposite proliferative behavior of Notch1-deficient hair follicle and epidermal keratinocytes.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
PTTG1 overexpression in adrenocortical cancer is associated with poor survival and represents a potential therapeutic target.
Sex, Age, Specimen part, Disease stage
View SamplesChronic obstructive pulmonary disease (COPD) is an inflammatory lung disease with complex pathological features and largely unknown etiologies. Identification and validation of biomarkers for this disease could facilitate earlier diagnosis, appreciation of disease subtypes and/or determination of response to therapeutic intervention. To identify gene expression markers for COPD, we performed genome-wide expression profiling of lung tissue from 56 subjects using the Affymetrix U133 Plus 2.0 array. Lung function measurements from these subjects ranged from normal, un-obstructed to severely obstructed. Analysis of differential expression between cases (FEV1<70%, FEV1/FVC<0.7) and controls (FEV1>80%, FEV1/FVC>0.7) identified a set of 65 probe sets representing discrete markers associated with COPD. Correlation of gene expression with quantitative measures of airflow obstruction (FEV1 or FEV1/FVC) identified a set of 220 probe sets. A total of 31 probe sets were identified that showed evidence of significant correlation with quantitative traits and differential expression between cases and controls.
Molecular biomarkers for quantitative and discrete COPD phenotypes.
Race
View SamplesBackground: Adrenocortical carcinoma (ACC) is associated with poor survival rates. The objective of the study was to analyze ACC gene expression profiling data prognostic biomarkers and novel therapeutic targets.
PTTG1 overexpression in adrenocortical cancer is associated with poor survival and represents a potential therapeutic target.
Sex, Disease stage
View SamplesAnalysis of gene expression by astrocytes or non-astrocyte cells in spinal cord injury (SCI) lesions may lead to the identification of molecules that impact on axon regrowth. We conducted genome-wide RNA sequencing of (i) immunoprecipitated astrocyte-specific ribosome-associated RNA (ramRNA) from WT or STAT3-CKO astrocytes, and (ii) the non-precipitated (flow-through) RNA deriving from non-astrocyte cells in the same tissue samples 14 days following SCI. DOI: 10.1038/nature17623 Overall design: Young adult female mGFAP-Cre-RiboTag or mGFAP-Cre-RiboTag-STAT3-LoxP mice underwent severe crush SCI at thoracic level 10. 14 days following SCI, the central 3mm of the SCI lesion was extracted, homogenized and (i) astrocyte-specific ribosome-associated RNA (ramRNA) precipitated via a hemagglutinin (HA) tag targeted to either WT (n=4) or STAT3-CKO (n=3) astrocytes, and (ii) the non-precipitated (flow-through) RNA deriving from non-astrocyte cells in the same tissue samples. Sex and age-matched mGFAP-Cre-RiboTag mice served as uninjured controls (n=4).
Astrocyte scar formation aids central nervous system axon regeneration.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
c-Jun promotes cell migration and drives expression of the motility factor ENPP2 in soft tissue sarcomas.
Specimen part, Cell line
View SamplesAffymetrix exon arrays to identify genes that were differentially expressed after c-Jun inhibition in LPS cell line with and with no Jun amplification.
c-Jun promotes cell migration and drives expression of the motility factor ENPP2 in soft tissue sarcomas.
Specimen part, Cell line
View SamplesWe assayed the effect of c-Jun overexpression on gene expression in the three DDLPS cell lines using RNA-Seq (Illumina). Overall design: 141, LPS12 and 510 has been overexpressed with c-Jun or control c-DNA and results were analyzed in high-througput sequencing metadata.
c-Jun promotes cell migration and drives expression of the motility factor ENPP2 in soft tissue sarcomas.
No sample metadata fields
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