A Japanese herbal medicine, Hochuekkito (TJ-41), has anti-inflammatory effects on the COPD mouse model
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE239537 | GEO | 2024/05/15
REPOSITORIES: GEO
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2022-01-01 | GSE153097 | GEO
Project description:Background: Chronic obstructive pulmonary disease (COPD) is a serious chronic disease of the airways that affects many people worldwide and have limited treatment options. While small animal models provide a platform for therapeutic investigations into COPD, their deficiencies continue to impede clinical translation. Alternatively, as a large animal model, sheep have a respiratory system anatomically and physiologically similar to that of humans, encouraging their use in airway disease research. The aim of this study was to better understand disease pathology in a large animal (sheep) experimental model of COPD. Methods: COPD was induced in sheep following lung exposure to porcine elastase (PE) and repeated weekly lung exposures to lipopolysaccharide (LPS) over a period of 8 weeks. Bronchoalveolar fluid and blood samples were collected for immune analyses. Lung function was assessed and lung tissues were collected for histopathology and RNA sequencing. Results: Lung neutrophil levels were elevated in response to repeated airway exposure to PE/LPS, accompanied by a significant decline in ventilation over time. Histological evidence of COPD-like disease changes included chronic inflammation with increased airway and tissue inflammation scores, together with significantly larger airway wall area measures, increased connective tissue deposition and dysregulated gene expression. Conclusions: These studies demonstrate sustained chronic airway inflammation and pathophysiological lung changes in a sheep model of COPD, providing many similarities to that seen in COPD patients. This work opens a pathway for future translational studies using this unique large animal model of COPD, which will serve to bridge the gap between smaller animal models and humans.
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2014-08-31 | E-GEOD-51227 | biostudies-arrayexpress
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Project description:Abstract<br>BACKGROUND: Gene expression profiling (GEP) in cells obtained from peripheral blood has demonstrated to be a very useful approach for biomarker discovery and for studying molecular pathogenesis of prevalent diseases. While there is limited literature availble on gene expression markers associated to Chronic Obstructive Pulmonary Disease (COPD), the transcriptomic picture associated to critical respiratory illness in this disease is not known to the present moment. <br>RESULTS: By using Agilent microarray chips, we have profiled gene expression signatures in whole blood of 28 COPD patients hospitalized with distinct degree of respiratory compromise.12 of them needed of admission to the ICU, while 16 were admitted to the Respiratory Medicine Service. GeneSpring GX 11.0 software was used for performing statistical comparison of transcript levels between ICU and non ICU patients. Ingenuity pathway analysis 8.5 (IPA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to select, annotate and visualize genes by function and pathway (gene ontology). T-test evidenced 1501 genes differentially expressed between ICU and non ICU patients. IPA and KEGG analysis of the most representative biological functions revealed that ICU patients showed increased levels of neutrohil gene transcripts, being [cathepsin G (CTSG)], [elastase, neutrophil expressed (ELANE)], [proteinase 3 (PRTN3)], [myeloperoxidase (MPO)], [cathepsin D (CTSD)], [defensin, alpha 3, neutrophil-specific (DEFA3)], azurocidin 1 (AZU1)], [bactericidal/permeability-increasing protein (BPI)] the most representative ones. Proteins codified by these genes form part of the azurophilic granules of neutrophils and are involved in both antimicrobial defence and tissue damage. This ?neutrophil signature? was paralleled by necessity of advanced respiratory and vital support, and presence of bacterial infection.<br>CONCLUSION: study of transcriptomic signatures in blood suggests a central role of neutrophil proteases in COPD patients with critical respiratory illness. Measurement / modulation of the expression of these genes could represent an option for clinical monitoring and treatment of severe COPD exacerbations. <br><br>Keywords: COPD, critical, expression, gene, microarray, neutrophil, proteases.<br><br>
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