We have previously demonstrated that pre-B-cell colony enhancing factor (PBEF) ais a biomarker in sepsis and sepsis-induced acute lung injury (ALI) with genetic variants conferring ALI susceptibility118. In the current study, we explored the mechanistic participation of PBEF in ALI and ventilator-induced associated lung injury (VIALI). Initial in vitro studies and demonstrated rhPBEF aas a direct rat neutrophil chemotactic factor in vitro producing marked in vivo increases in BAL leukocytes (PMNs) in vivo following (intratracheal injection (,IT) in C57B6 mice. These latter changes were accompanied by increased BAL levels of the PMN chemoattractants (, KC and MIP2), and modest changes in lung vascular and but were not associated with significant increasesin alveolar permeability. We next explored the potential synergism between rhPBEF administration (IT) and a mechanical ventilation model of modest VILI lung injury (4 hours, 30 ml/kg tidal volume). We and observed dramatic synergistic increases in BAL PMNs, and both BAL protein and cytokine levels (IL-6, TNF-?, KC). Gene expression profiling Microarray analysis further supported a major role for PBEF in the induction of gene modules associated with ALI and VALI (NFkB pathway, leukocyte extravasation, apoptosis, toll receptor signaling). Finally, we exposed wild type and heterozygous PBEF+/- mice (targeted deletion of a single PBEF allele deletion) to a model of severe VILImechanical ventilation-induced lung injury (4 hours, 40 ml/kg tidal volume). PBEF+/- mice were significantly protected from VIALI-associated increases in BAL protein and BAL IL-6 levels and exhibited significantly reduced expression of ALI-associated gene expression modules. Together, these results indicate that PBEF is a key inflammatory mediator intimately involved in both the development and severity of ventilator-induced ALI.
Essential role of pre-B-cell colony enhancing factor in ventilator-induced lung injury.
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View SamplesParticulate Matter Triggers Carotid Body Dysfunction, Respiratory Dysynchrony and Cardiac Arrhythmias in Mice with Cardiac Failure
Particulate matter induces cardiac arrhythmias via dysregulation of carotid body sensitivity and cardiac sodium channels.
Age, Specimen part
View SamplesBackground: Microvascular injury and increased vascular leakage are prominent features of the radiation-induced lung injury (RILI) which follows cancerassociated thoracic irradiation. The mechanisms of RILI are incompletely understood and therapeutic strategies to limit RILI are currently unavailable. We established a murine model of radiation pneumonitis in order to assess mechanism-based therapies for RILI-induced inflammation and vascular barrier dysfunction. Based on prior studies, we investigated the therapeutic potential of simvastatin as a vascular barrier protective agent in RILI.
Simvastatin attenuates radiation-induced murine lung injury and dysregulated lung gene expression.
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View SamplesWe used microarrays to compare the global programme of gene expression in primary cultures of neurons and astrocytes. These data sets were compared to the expression profiles of other tissues, including pancreatic islets, in order to identify a specific neuroendocrine program in pancreatic islets.
Glucose regulation of a cell cycle gene module is selectively lost in mouse pancreatic islets during ageing.
Specimen part
View SamplesProper functioning of tissues requires cells to behave in uniform, well-organized ways. Conversely, many diseases involve increased cellular heterogeneity due to genetic and epigenetic alterations. Defining the mechanisms that counteract phenotypic variability is therefore critical to understand how tissues sustain homeostasis. Here, we carried out a single-cell resolution screen of zebrafish embryonic blood vessels upon mutagenesis of single microRNA (miRNA) genes and multi-gene miRNA families. We found that miRNA mutants exhibit a profound increase in cellular phenotypic variability of specific vascular traits. Genome-wide analysis of endothelial miRNA target genes identified antagonistic regulatory nodes of vascular growth and morphogenesis signaling that allow variable cell behaviors when derepressed. Remarkably, lack of such miRNA activity greatly sensitized the vascular system to microenvironmental changes induced by pharmacological stress. We uncover a previously unrecognized role of miRNAs as a widespread protective mechanism that limits variability in cellular phenotypes. This discovery marks an important advance in our comprehension of how miRNAs function in the physiology of higher organisms. Overall design: Analysis of differential genes expression in Zebrafish endothelial cells for 4 different developmental stages
MicroRNAs Establish Uniform Traits during the Architecture of Vertebrate Embryos.
No sample metadata fields
View SamplesThe lung host immune responses following M.tuberculosis infection in the mouse model of tuberculosis were assayed by studying the gene expression profiles at day 0, day 12, 15 and 21 post infection
Profiling early lung immune responses in the mouse model of tuberculosis.
Specimen part, Time
View SamplesThis study describes a cDNA microarray analysis that compared developing mouse MyoD-/- limb musculature (MyoD-dependent, innervated by Lateral Motor Column motor neurons) and Myf5-/- back (epaxial) musculature (Myf5-dependent, innervated by Medial Motor Column motor neurons) to the control and to each other, at embryonic day 13.5 which coincides with the robust programmed cell death of motor neurons and the inability of myogenesis to undergo its normal progression in the absence of Myf5 and MyoD that at this embryonic day cannot substitute for each other.
Role of skeletal muscle in motor neuron development.
Specimen part
View SamplesIKKbeta is a subunit of the IkB kinase (IKK) complex required for NF-kB activation in response to pro-inflammatory signals. NF-kB regulates the expression of many genes involved in inflammation, immunity and apoptosis, and also controls cell proliferation and differentiation in different tissues; however, its function in skin physiopathology remains controversial. We here report the alterations caused by increased IKKbeta activity in basal cells of the skin of transgenic mice.
IKKbeta leads to an inflammatory skin disease resembling interface dermatitis.
Sex, Age, Specimen part
View SamplesPURPOSE To identify retinal genes and their relevant expression pathways affected by intravitreal injections of dexamethasone and triamcinolone acetonide in mice at clinically relevant time points for patient care.
In vivo gene expression profiling of retina postintravitreal injections of dexamethasone and triamcinolone at clinically relevant time points for patient care.
Sex, Specimen part
View SamplesWe found that a number of Tfh cells downmodulated BCL6 protein after their development, and we sought to compare the gene expression between BCL6-hi Tfh cells and BCL6-low Tfh cells.
Bcl6 protein expression shapes pre-germinal center B cell dynamics and follicular helper T cell heterogeneity.
Specimen part
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