Validation of mRNA markers differentiating among human ARDS subgroups in an ovine model of ARDS phenotypes
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PROVIDER: PRJNA852569 | ENA |
REPOSITORIES: ENA
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Project description:Comparison of a subset of mRNA markers previously discribed in leukocytes of human ARDS patients with lung tissue expression in ovine ARDS phenotype 1 and phenotype 2 models
2022-07-27 | GSE206888 | GEO
Project description:BackgroundThe discovery of biological subphenotypes in acute respiratory distress syndrome (ARDS) might offer a new approach to ARDS in general and possibly targeted treatment, but little is known about the underlying biology yet. To validate our recently described ovine ARDS phenotypes model, we compared a subset of messenger ribonucleic acid (mRNA) markers in leukocytes as reported before to display differential expression between human ARDS subphenotypes to the expression in lung tissue in our ovine ARDS phenotypes model (phenotype 1 (Ph1): hypoinflammatory; phenotype 2 (Ph2): hyperinflammatory).MethodsWe studied 23 anesthetized sheep on mechanical ventilation with observation times between 6 and 24 h. They were randomly allocated to the two phenotypes (n = 14 to Ph1 and n = 9 to Ph2). At study end, lung tissue was harvested and preserved in RNAlater. After tissue homogenization in TRIzol, total RNA was extracted and custom capture and reporter probes designed by NanoString Technologies were used to measure the expression of 14 genes of interest and the 6 housekeeping genes on a nCounter SPRINT profiler.ResultsAmong the 14 mRNA markers, in all animals over all time points, 13 markers showed the same trend in ovine Ph2/Ph1 as previously reported in the MARS cohort: matrix metalloproteinase 8, olfactomedin 4, resistin, G protein-coupled receptor 84, lipocalin 2, ankyrin repeat domain 22, CD177 molecule, and transcobalamin 1 expression was higher in Ph2 and membrane metalloendopeptidase, adhesion G protein-coupled receptor E3, transforming growth factor beta induced, histidine ammonia-lyase, and sulfatase 2 expression was higher in Ph1. These expression patterns could be found when different sources of mRNA - such as blood leukocytes and lung tissue - were compared.ConclusionIn human and ovine ARDS subgroups, similar activated pathways might be involved (e.g., oxidative phosphorylation, NF-κB pathway) that result in specific phenotypes.
| S-EPMC9295897 | biostudies-literature
Project description:Rat model of ARDS was induced by saline lavage and mechanical ventilation. miRNA from rat lungs were used for dual color DNA microarray hybridization with 3DNA 50 kit version 2. Two-condition experiment, CON vs. ARDS lung tissues. replicates: 6 control, 6 ARDS. One replicate per array.
2014-05-07 | E-GEOD-57223 | biostudies-arrayexpress
Project description:Rat model of ARDS was induced by saline lavage and mechanical ventilation. Total RNA from rat lungs were used for dual color DNA microarray hybridization with 3DNA 50 kit version 2. Two-condition experiment, CON vs. ARDS lung tissues. replicates: 5 control, 7 ARDS. One replicate per array.
2014-04-24 | E-GEOD-57011 | biostudies-arrayexpress
Project description:Mannheimia haemolytica strain:ovine | isolate:ovine Genome sequencing and assembly
| PRJNA1040763 | ENA
Project description:We aimed to identify endotypes of pediatric acute respiratory distress syndrome (ARDS) using whole blood transcriptomics collected within 24 hours of Berlin ARDS onset in intubated children from CHOP Affy microarray and cluster analysis
2020-04-02 | GSE147902 | GEO
Project description:Clinical study of critically ill patients with sepsis and sepsis-related ARDS with whole blood RNA collected within the first 24 hours of admission Goal of the study was to determine whether biologically relevant genes were identified to be differentially expressed genes in patients with sepsis alone and sepsis with ARDS Prospective observational study, case cohort design
2015-04-01 | E-GEOD-66890 | biostudies-arrayexpress
Project description:The objective of this study was to determine if nasal transcriptomics could be used to characterize the underlying pathobiology and predict clinical course of patients with pediatric ARDS (PARDS). Subjects meeting consensus PARDS criteria or controls admitted to the Pediatric ICU without lung disease had nasal cytology brushings on days 1, 3, 7 and 14. The gene expression of these brushings was compared to identify subtypes and describe clinical course. Concurrent nasal and bronchial brushings were collected if bronchoscopy was performed. We identified four PARDS subgroups, termed A, B, C, and D. Subgroup B was marked by inflammation and ciliary cell dysfunction. Subgroup D was marked by reduced epithelial stem cell mRNAs without inflammation. Subgroup A had hypo-inflammation and upregulation of pathways important in epithelial cell repair. Subgroup C had increased ciliary cell genes. Control specimens almost entirely clustered with Subgroup C, but one that developed PARDS clustered with Subgroup B and several that developed lung injury clustereced with Subgroups B and A. Over time, Subgroups D and B transitioned to A which transitioned to C. Bronchial and nasal gene expresison were similar.
2021-12-24 | GSE192364 | GEO
Project description:SARS-CoV-2 is a novel coronavirus that causes acute respiratory distress syndrome (ARDS), death and long-term sequelae. Innate immune cells are critical for host defense but are also the primary drivers of ARDS. The relationships between innate cellular responses in ARDS resulting from COVID-19 compared to other causes of ARDS, such as bacterial sepsis is unclear. Moreover, the beneficial effects of dexamethasone therapy during severe COVID-19 remain speculative, but understanding the mechanistic effects could improve evidence-based therapeutic interventions. To interrogate these relationships, we developed an scRNAseq atlas that is freely accessible (biernaskielab.ca/COVID_neutrophil). We discovered that compared to bacterial ARDS, COVID-19 was associated with distinct neutrophil polarization characterized by either interferon (IFN) or prostaglandin (PG) active states. Neutrophils from bacterial ARDS had higher expression of antibacterial molecules such as PLAC8 and CD83. Dexamethasone therapy in COVID patients rapidly altered the IFNactive state, downregulated interferon responsive genes, and activated IL1R2+ve neutrophils. Dexamethasone also induced the emergence of immature neutrophils expressing immunosuppressive molecules ARG1 and ANXA1, which were not present in healthy controls. Moreover, dexamethasone remodeled global cellular interactions by changing neutrophils from information receivers into information providers. Importantly, male patients had higher proportions of IFNactive neutrophils and a greater degree of steroid-induced immature neutrophil expansion. Indeed, the highest proportion of IFNactive neutrophils was associated with mortality. These results define neutrophil states unique to COVID-19 when contextualized to other life-threatening infections, thereby enhancing the relevance of our findings at the bedside. Furthermore, the molecular benefits of dexamethasone therapy are also defined. The identified molecular pathways can now be targeted to develop improved therapeutics.
2021-10-05 | PXD028429 | Pride