ABSTRACT Background: Viral myocarditis is a life-threatening illness that may lead to heart failure or cardiac arrhythmias. This study examined whether human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) could be used to model the pathogenic processes of coxsackievirus-induced viral myocarditis and to screen antiviral therapeutics for efficacy. Methods and Results: Human iPSC-CMs were infected with a luciferase-expressing mutant of the coxsackievirus B3 strain (CVB3-Luc). Brightfield microscopy, immunofluorescence, and calcium imaging were used to characterize virally infected hiPSC-CMs. Viral proliferation on hiPSC-CMs was subsequently quantified using bioluminescence imaging. For drug screening, select antiviral compounds including interferon beta 1 (IFN1), ribavirin, pyrrolidine dithiocarbamate (PDTC), and fluoxetine were tested for their capacity to abrogate CVB3-Luc proliferation in hiPSC-CMs in vitro. The ability of some of these compounds to reduce CVB3-Luc proliferation in hiPSC-CMs was consistent with the reported drug effects in previous studies. Finally, mechanistic analyses via gene expression profiling of hiPSC-CMs infected with CVB3-Luc revealed an activation of viral RNA and protein clearance pathways within these hiPSC-CMs after IFN1 treatment. Conclusions: This study demonstrates that hiPSC-CMs express the coxsackievirus and adenovirus receptor, are susceptible to coxsackievirus infection, and can be used to confirm antiviral drug efficacy. Our results suggest that the hiPSC-CM/CVB3-Luc assay is a sensitive platform that could be used to screen novel antiviral therapeutics for their effectiveness in a high-throughput fashion.
Human induced pluripotent stem cell-derived cardiomyocytes as an in vitro model for coxsackievirus B3-induced myocarditis and antiviral drug screening platform.
Specimen part, Treatment
View SamplesMethylene diphenyl diisocyanate is a chemical known to cause asthma. The present study uses mice to investigate exposure-induced changes in lung gene expression and effects of a chloride channel inhibitor
Analysis of Lung Gene Expression Reveals a Role for Cl<sup>-</sup> Channels in Diisocyanate-induced Airway Eosinophilia in a Mouse Model of Asthma Pathology.
Sex
View SamplesWe hypothesized that gene expression in lungs of Fra-1+/+ and Fra-1-/- mice are divergent thus contributing fibrosis. More specifically, Fra-1-/- mice are increased susceptible to fibrosis. In order to test these hypotheses at the gene expression level, we utilized microarray analysis to examine transcriptional differences between Fra-1+/+ and Fra-1-/- mice at early time point.
Expression profiling of genes regulated by Fra-1/AP-1 transcription factor during bleomycin-induced pulmonary fibrosis.
Sex, Age, Specimen part
View SamplesRATIONALE: Mechanical ventilation (MV) is an indispensable therapy for critically ill patients with acute lung injury and the adult respiratory distress syndrome. However, the mechanisms by which conventional MV induces lung injury remain unclear. OBJECTIVES: We hypothesized that disruption of the gene encoding Nrf2, a transcription factor which regulates the induction of several antioxidant enzymes, enhances susceptibility to ventilator-induced lung injury (VILI), while antioxidant supplementation attenuates such effect. METHODS: To test our hypothesis and to examine the relevance of oxidative stress in VILI, here we have assessed lung injury and inflammatory responses in Nrf2-deficient (Nrf2(-/-)) mice and wildtype (Nrf2(+/+)) animals following acute (2 h) injurious model of MV with or without administration of antioxidant. MEASUREMENTS AND MAIN RESULTS: Nrf2(-/-) mice displayed greater levels of lung alveolar and vascular permeability and inflammatory responses to MV as compared to Nrf2(+/+) mice. Nrf2-deficieny enhances the levels of several pro-inflammatory cytokines implicated in the pathogenesis of VILI. We found diminished levels of critical antioxidant enzymes and redox imbalance by MV in the lungs of Nrf2(-/-) mice; however antioxidant supplementation to Nrf2(-/-) mice remarkably attenuated VILI. When subjected to clinically relevant prolong period of MV, Nrf2(-/-) mice displayed greater levels of VILI than Nrf2(+/+) mice. Expression profiling revealed lack of induction of several VILI genes, stress response and solute carrier proteins and phosphatases in Nrf2(-/-) mice. CONCLUSIONS: Collectively, our data demonstrate for the first time a critical role for Nrf2 in VILI, which confers protection against cellular responses induced by MV by modulating oxidative stress.
Genetic and pharmacologic evidence links oxidative stress to ventilator-induced lung injury in mice.
No sample metadata fields
View SamplesWe hypothesize that gene expression in the Type II cells of Nrf2+/+ and Nrf2-/- mice are divergent thus contributing the cell growth. More specifically, type II cells from Nrf2-/- mice have increased reactive oxygen species that cause the impaired cell growth. In order to test these hypotheses at the gene expression level, we utilized microarray analysis to examine transcriptional differences between Nrf2+/+ and Nrf2-/- cells.
Genetic dissection of the Nrf2-dependent redox signaling-regulated transcriptional programs of cell proliferation and cytoprotection.
No sample metadata fields
View SamplesAnalysis of genes regulated by STC1 down-regulation in mouse 4T1 derived clone, 4T1ch9. STC1 expression is associated with tumor growth and metastasis. This study looks at genes affected when STC1 expression is down-regulated by STC1 shRNA.
STC1 expression is associated with tumor growth and metastasis in breast cancer.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide transcriptomic analysis of cotton under drought stress reveal significant down-regulation of genes and pathways involved in fibre elongation and up-regulation of defense responsive genes.
Specimen part, Treatment
View SamplesTranscriptome analysis in cotton during fibre development stages.
Genome-wide transcriptomic analysis of cotton under drought stress reveal significant down-regulation of genes and pathways involved in fibre elongation and up-regulation of defense responsive genes.
Treatment
View SamplesTranscriptome analysis in cotton under drought stress.
Genome-wide transcriptomic analysis of cotton under drought stress reveal significant down-regulation of genes and pathways involved in fibre elongation and up-regulation of defense responsive genes.
Specimen part, Treatment
View SamplesPurpose: We aimed to identify miRNAs which are induced by the Activin/Nodal effectors, P-Smad2/3, in order to further our understanding of how P-Smad2/3 controls downstream gene expression in mouse ES cells to regulate crucial biological processes. Methods: We used a previously developed Tetracycline-On (Tet-On) system (TAG1) to manipulate the levels of P-Smad2/3 in mouse ES cells and performed an Illumina deep-sequencing screen to identify miRNAs which followed the P-Smad2/3 pathway. Results: We filtered the deep-seq data to identify a list of 28 miRNAs which showed a >1.25 fold increase in response to P-Smad2/3 induction and a >1.25 fold decrease in response to P-Smad2/3 repression. Conclusions: Our study represents a comprehensive global profiling of miRNA expression in response to changes in P-Smad2/3 levels in mouse ES cells. Overall design: miRNA profiles of TAG1 cells which were untreated (control), SB-431541 treated (P-Smad2/3 repressed), or Dox treated (P-Smad2/3 induced), were generated using Illumina GAII.
TGF-β/Smad2/3 signaling directly regulates several miRNAs in mouse ES cells and early embryos.
Specimen part, Subject
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